How To Lower High Blood Pressure Naturally

High Blood Pressure Exercise Program

Natural Blood Pressure is a comprehensive program that helps people lower, control the high blood pressure in the most effective way. By plain explanation as well as instruction, Christian Goodman (Blue Heron), the creator of Natural Blood Pressure will drop your blood pressure to normal in less than a week. If this pressure is too high, it puts a strain on your arteries and your heart making you more likely suffer a heart attack, a stroke or kidney disease. All of your risk will be stopped instantly in less than 30 minutes a day to practice exercises. These exercises used in Natural Blood Pressure are focused on mind and body ones in the system called Focused Break. The Blue Heron Health News blood pressure program does seem to work. I would recommend it to anyone suffering from high blood pressure or hypertension because, it will not interfere with any existing medications, is easy to implement, stimulates relaxation and reduces stress levels. Continue reading...

High Blood Pressure Exercise Program Summary


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Atr Gene Polymorphisms And Hypertension

Hypertension has a multifactorial etiology with a strong genetic component. Of many human candidate gene loci examined, those encoding components of the RAS are considered to be among the most plausible candidates. The association of renin gene polymorphism with essential hypertension has been scarcely reported (16). On the contrary, several studies have demonstrated a link between the angiotensinogen (AG) gene and hypertension (17-19), particularly the M235T variant which correlates with both plasma angiotensinogen concentration and elevated BP variation nevertheless, large ethnic discrepancies make this genotyping difficult to use. The cloning of ACE gene enabled the detection of many polymorphisms (20,21), one of which consists of the presence (insertion allele I) or absence (deletion allele D) of a 287-bp DNA fragment in intron 16 of the ACE gene. A strong association was detected between the alleles of this polymorphism and the level of serum ACE, individuals ho-mozygous for the...

Approach To Hypertension

Essential hypertension Also known as idiopathic or primary hypertension. It has no known cause, yet it comprises approximately 95 of all cases of hypertension. Lifestyle modification A cornerstone in the treatment of hypertension, consisting of regular aerobic activity, weight loss, decreased salt intake, and increased intake of fruit and vegetables, while decreasing the amount of total fat. especially saturated fat, in the diet. Alcohol consumption should be moderated, no more than two glasses of wine per day for men and one glass per day for women. Prehypertension Blood pressures 120-139 80-89 mmHg Stage I hypertension Blood pressures 140-159 90-99 mmHg Stage II hypertension Blood pressures 160 100 mmHg Secondary hypertension Elevated arterial blood pressure with a known underlying cause, such as renal artery stenosis or primary aldosteronism. Prevalence is approximately 5-6 of all cases of hypertension. Hypertension can first be staged, to guide the intensity of medical...

Hypertension and Toxemia of Pregnancy

Toxemia is characterized by extreme hypertension, protein loss in the urine, and fluid retention and can be fatal for the mother and or the fetus.17 Fortunately, optimal nutrition can help prevent this disorder. Both too much and too little weight gain increase risk of hypertension during pregnancy. Inadequate salt intake may also increase the risk, so women should not attempt to restrict salt intake during pregnancy. Low calcium and or zinc intake sharply increases risk of toxemia. Calcium supplementation (2g day) during pregnancy may reduce risk of toxemia by a third (see Fig. 4.5).17 Supplemental vitamin B6 (25-50 mg day) and evening primrose oil (containing gLa) (see pp.89) may also be helpful in preventing and or treating this disorder.

Role Of Agt In Hypertension

The RAS plays an important role in the regulation of BP. The octapeptide, angiotensin II (Ang II), is one of the most active vasopressor agents and is obtained by the proteolytic cleavage of a larger precursor molecule, angiotensinogen (AGT), which is primarily synthesized in the liver and to a lesser extent in the kidney, brain, heart, adrenal, fat, and vascular walls. The human AGT cDNA is 1455 nucleotides long and codes for a 485-amino acid protein (9). AGT is first converted by renin to produce a decapeptide, Ang I, and is then converted to Ang II by the removal of a C-terminal dipeptide by ACE (10). In experimental as well as clinical studies, chronic administration of renin-angiotensin inhibitors has proven effective in lowering BP in hypertension. Genes that encode components of the RAS are therefore potential candidate genes that may play a role in the regulation of BP. The plasma concentration of AGT is close to the Michaelis constant of the enzymatic reaction between renin...

Urotensin Expression in Hypertension and Heart Failure

Contracting human coronary, mammary, and radial arteries in responding tissue however, some samples fail to respond to urotensin but are reactive toward ET-1 (69). These results demonstrate binding of urotensin to the urotensin receptor in the human vasculature. Urotensin gene expression is abundant in the human kidney and atrium and throughout the vasculature (70). Urine levels of urotensin are significantly higher in hypertensive compared with normotensive individuals and suggest that the kidney may produce urotensin in hypertension. A role for urotensin in essential hypertension has been confirmed in a study by Cheung et al. (71), which showed that plasma levels of urotensin are significantly higher in hypertensive patients compared with normotensive subjects and correlate with systolic BP.

Antihypertensive Drugs

A number of large clinical trials have investigated differences in the efficiency of older versus newer antihypertensive drug strategies. In general, no clear-cut differences are detectable between the various classes of antihypertensive drugs, although this statement is a matter of ongoing dispute. In initiating drug treatment, therapy should always be started gently, and target blood pressure will not generally be achieved within the first months. An important modern principle of drug treatment is to attempt combination therapy early on. Many experts recommend a low dose of a single drug as the primary approach, and if blood pressure control is not achieved, to add a low dose of a different agent, rather than increasing the dose of the first compound. The reason for this strategy is to diminish the possibility of eliciting adverse effects of the drugs. It is essential to keep in mind that antihypertensive therapy must remain operational for many years, even decades, in most...

M235t Polymorphism Of Agt Gene And Hypertension

The AGT gene contains five exons and four introns, which span 13 kb (18). An extensive study of the potential role of the AGT gene in human essential hypertension was performed on two large series of hypertensive siblingships yielding 379 sibling pairs. The highly polymorphic CA dinucleotide repeat marker located in the 3'-region of the AGT gene and the powerful affected sibling pair methodology were used to obtain evidence of a genetic linkage between the AGT gene and hypertension in this study (19). A 17 excess of AGT allele sharing was found in severely hypertensive sibling pairs. Whereas significant linkage was obtained in male pairs in both the Utah and Paris groups, no excess of shared AGT alleles was observed in female subjects, suggesting the influence of an epistatic hormonal phenomenon. These studies also showed that variants 235T and 174M of the AGT gene are associated with hypertension. From these studies, it was estimated that mutations at the AGT locus might be a...

Unwanted Interactions With Antihypertensive Drugs

Alcohol intake is the commonest contributing factor, or even cause of hypertension, and should always be considered as a cause of erratic or failed Prostaglandin synthesis. Nonsteroidal anti-inflammatory drugs (NSAIDs), e.g. indomethacin, attenuate the antihypertensive effect of -adrenoceptor blockers and of diuretics, perhaps by inhibiting the synthesis of vasodilator renal prostaglandins. This effect can also be important when a diuretic is used for severe left ventricular failure. Pharmacological antagonism. Sympathomimetics, e.g. amphetamine, phentolamine (present in anorectics and cold and cough remedies) may lead to loss of antihypertensive effect, and indeed to a hypertensive reaction when taken by a patient already on a -adrenoceptor blocker, due to unopposed a-adrenergic stimulation. Surgical anaesthesia may lead to a brisk fall in blood pressure in patients taking antihypertensives. Antihypertensive therapy should not be routinely altered before surgery, although it...

Basic Tests For Initial Evaluation Of Hypertension

Initial therapy should be based on the stage or degree of hypertension. For all patients with hypertension, lifestyle modifications should be instituted. For those with prehypertension (blood pressure 120-139 80-89 mmHg), lifestyle modifications are the only interventions indicated unless they have another comorbid condition, such as heart failure or diabetes, which necessitates use of an antihypertensive. Patient with stage I hypertension (blood pressure 140-159 90-99 mmHg) should be started on a single antihypertensive agent, whereas those with stage II hypertension (blood pressure 160 mmHg 100 mmHg) will need at least two antihypertensives in combination.

Treatment of Hypertension

Hypertension is a major risk factor for PAD, but data are not available to clarify whether treatment will alter the progression of the disease or the risk of claudication. Beta-adrenergic-antagonist drugs have been thought to have unfavorable effects on symptoms in patients with PAD. This concern arose from several early case reports of worsening claudication and decreases in blood flow in the legs in patients taking these drugs. A meta-

Genomewide Analysis To Identify Hypertensionrelated Genes

Krushkal et al. (3) performed a genome-wide linkage analysis of systolic BP on 427 sibling pairs and identified four regions of the human genome that show statistical significant linkage. These regions are on chromosomes 2, 5, 6, and 15. These chromosomal regions include numerous potential candidates, such as phospholamban, estrogen receptor (ER), aminopeptidase N, a lB-adrenergic receptor, dopamine receptor type 1A (DR-1A), calmodulin, and sodium-calcium exchanger. However, none of these genes has been confirmed to be associated with human hypertension. Hunt et al. (4) performed a genome-wide analysis using 2959 individuals in 500 white families from the National Heart, Lung and Blood Institute (NHLBI) family heart study and identified five regions of the genome with logarithm of odds (LOD) scores higher than 2.0 for hypertension. These included chromosomes 1, 7, 12, and 15. On the other hand, chromosome 6 showed the best evidence for linkage with systolic BP (SBP). It is important...

Association Of The 217a Variant Of Agt Gene With Hypertension

Because hypertension is more common in African-American subjects, our laboratory is interested in understanding molecular mechanisms involved in hypertension in the African-American population. We have therefore analyzed 186 African-American and 127 Caucasian subjects with hypertension (mean age 59 10 yr) and 156 African-American and 135 Caucasian normotensive controls (mean age 58 10 yr). All of these subjects were recruited from the outpatient department of The State University of New York Health Science Center in Brooklyn, New York and Westchester Medical Center, Valhalla, New York. All case and control subjects gave informed consent before participating in the research. All cases were diagnosed as having primary hypertension and patients with secondary hypertension, diabetes mellitus, or ischemic heart disease were excluded. The criteria for hypertension was defined as a SBP greater than 140 mmHg, a DBP greater than 90 mmHg, or under antihypertensive therapy. BP was measured twice...

Secondary Causes Of Hypertension

Smoking, dyslipidemia, diabetes mellitus, obesity, kidney disease, and a family history of premature cardiovascular disease. Target organ damage of hypertension includes cardiomyopathy, nephropathy, and retinopathy. Although treatment decisions in the management of hypertension depend more upon the blood pressure level (modified perhaps in the presence of diabetes mellitus), the presence of other cardiovascular risk factors and or evidence of target organ damage may further guide therapy and provide some prognostic information. A complete history and physical examination, including funduscopic examination, auscultation of the major arteries for bruits, palpation of the

Pulmonary hypertension

Pulmonary hypertension is defined as a chronic increase in pulmonary artery systolic pressure above 30 mm Hg or a mean pressure greater than 20-25 mm Hg. From a consideration of Poiseuille's equation (page 187) it is apparent that pulmonary hypertension may be expected to occur in the following circumstances The clinical conditions that may cause pulmonary hypertension are listed in the box. For convenience these are grouped under five main headings It will, however, become apparent that such a categorisation is somewhat artificial for there are often a number of factors contributing to the hypertension in each patient.

Pulmonary venous hypertension

Pulmonary venous hypertension may be caused by mediastinal lesions which compress the pulmonary veins, a myxoma or ball-valve thrombus in the left atrium, mitral or aortic valve disease, or left ventricular failure. It may also result from pulmonary veno-occlusive disease.

Role of pulmonary vasodilators in pulmonary hypertension

The most obvious effect of pulmonary hypertension is that it increases the right ventricular pressure, workload, and oxygen consumption, and so may lead to right ventricular failure. As the blood flow to the right ventricle occurs during both systole and diastole it is important to maintain a high systemic pressure to minimise myocardial ischaemia. A second problem resulting from a high pulmonary artery pressure is that it may cause high pressure pulmonary oedema by increasing the pressure in the precapillary vessels. Pulmonary venous hypertension also causes oedema and in both situations severe arterial hypoxaemia may result. Pulmonary embolism and other conditions causing chronic hypertension may cause a maldistribution of blood flow as a result of changes in arteriolar resistance. Localised reductions in flow result in non-perfused alveoli and an increase in alveolar dead space, but the concomitant increases in pressure may also oppose the effects of hypoxic vasoconstriction, which...

Tissue Kallikrein In Hypertension

A dominant gene expressed as renal or urinary kallikrein may be associated with a reduced risk of hypertension (16). This finding suggests that high urinary kallikrein may have a protective effect against the development of high blood pressure. Reduced urinary kallikrein excretion has also been described in a number of genetically hypertensive rat models such as spontaneously hypertensive rats (SHR), New Zealand rats, Fawn-Hooded rats, and Dahl salt-sensitive (DSS) hypertensive rats (1721). Kinin appears to play a role in blood pressure regulation in SHR fed a salt-deficient diet, because the administration of a BK antagonist caused an increase in blood pressure (22). Furthermore, kininogen-deficient (Brown Norway-Katholiek) rats, which cannot generate kinin, are susceptible to the development of salt-induced hypertension (23). Several restriction fragment length polymorphisms have been mapped in the rat tissue kallikrein gene, and their regulatory regions have been identified in the...

Drugs used in hypertension and angina

Two groups of drugs, (3-adrenergic blockers and calcium channel blockers, are used in both hypertension and angina. Several drugs for hypertension are used also in the treatment of heart failure. Diuretics, particularly the thiazides, are useful antihypertensives. They cause an initial loss of sodium with a parallel contraction of the blood and extracellular fluid volume. The effect may reach 10 of total body sodium but it is not maintained. After several months of treatment, the main blood pressure lowering effect appears to reflect a reduced responsiveness of resistance vessels to endogenous vasoconstrictors, principally noradrenaline. While this hyposensitivity may be a consequence of the sodium depletion, thiazides are generally more effective antihypertensive agents than loop diuretics, despite causing less salt loss, and evidence suggests an independent action of thiazides on an unidentified ion-channel on vascular smooth muscle cell membranes. Maximum effect on blood pressure...

Treating Hypertension

A simple stepped regimen in keeping with the 1999 British Hypertension Society guidelines30 is the AB CD schema illustrated in Figure 23.2 33 3. If the blood pressure is still not controlled, a second agent should be added, using the opposite pair to the first drug e.g. if the patient is on an ACE inhibitor add a Calcium channel blocker or thiazide Diuretic (A+C or A+D), since both vasodilatation or diuresis will stimulate the renin-angiotensin system and turns nonrenin-dependent hypertension into renin-dependent hypertension). The combination B+D is associated with increased risk of diabetes and should be avoided in at-risk patients (obesity, family history). The combinations A+B or C+D usually produce a less than additive effect on blood pressure, but should be tried in patients still uncontrolled on more standard combinations. AB CD Rule for optimisation of antihypertensive treatment

Pregnancy Hypertension

Effective treatment of pregnancy-induced hypertension improves fetal and perinatal survival. There is a lack of good clinical trial evidence on which to base recommendations of one agent over another. Instead, drug usage reflects longevity of use without obvious harm to the fetus. Hence methyldopa is still the drug of choice for many obstetricians.35 Calcium-channel blockers (especially nifedipine) are common second-line drugs parenteral hydralazine is reserved for emergency reduction of blood pressure in late pregnancy, preferably in combination with a (3-blocker to avoid unpleasant tachycardia. (3-blockers (labetalol and atenolol) are often effective and are probably the drugs of choice in the third trimester there is anecdotal evidence to suggest growth retardation with p-blockade used in first and second trimester. Diuretics reduce the chance of developing pre-eclampsia, but are avoided in pre-eclampsia itself because these patients already have a contracted circulatory volume....

Hypertension in Hemodialysis Patients

Hypertension occurs in 90 of patients starting hemodialysis and persists in 70-90 of hemodialysis patients in the US 57 . In the large, multicenter Hemodialysis (HEMO) Study more than 70 of patients were hypertensive by JNC VI guidelines, and almost 75 required antihypertensive medications 58 . This is contrary to the situation in the late 1960s, when strict control of true dry body weight was practiced and the majority of patients did not require antihypertensive agents 59 . There is a consensus that most patients on dialysis have volume-dependent hypertension. Only a small proportion of patients have vasoconstrictive hypertension requiring bilateral nephrectomy in the past 59 or blood The possibility of controlling blood pressure in a reno-prival state by drastic reduction in dietary salt intake was first shown by Kempner 60, 61 in the 1940s. It was subsequently shown that the beneficial effect of the 'rice diet' on hypertension was related to the lowering of plasma volume and...

Table 93 Causes Of Hypertension

Essential hypertension (90 to 95 ) - age, race, and socioeconomic status Secondary hypertension (5 to10 ) has led some investigators to suggest that the basic underlying defect in hypertensive patients is an inability of the kidneys to adequately handle sodium. Increased sodium retention could account for the increase in blood volume. Indeed, many excellent experimental studies as well as clinical observations have shown that impaired renal natriuresis (sodium excretion) can lead to chronic hypertension. Besides the renal involvement in hypertension, it is well known that vascular changes can contribute to hypertensive states, especially in the presence of impaired renal function. For example, essential hypertension is usually associated with increased systemic vascular resistance caused by a thickening of the walls of resistance vessels and by a reduction in lumen diameters. In some forms of hypertension, this is mediated by enhanced sympathetic activity or by increased circulating...

Endothelin in hypertension and proatherogenic states

The role of renal endothelin receptors in diseases associated with hypertension appears to be critical. Hirata and colleagues 184 utilized the IPRK to demonstrate that ETB receptor stimulation induced release of nitric oxide. They found that ET-1 and ET-3 released nitric oxide via ETB receptors in renal vessels. ETB receptors were downregulated in deoxycorticosterone acetate (DOCA-salt) rat kidneys explaining why ETB-mediated NO release was reduced in DOCA-salt rats, an event which may modulate renal function and blood pressure regulation in DOCA-salt hypertensive rats. They subsequently observed that expression of ETB receptors in the endothelium was decreased in IPRK from 3 disease models (rats with hypertension, diabetes mellitus, and hypercholesterolemia) compared with that in the vascular smooth muscle cell 135 . Infusion of a highly selective ETB receptor agonist, BQ-3020, reduced renal perfusion pressure in Dahl salt-resistant rats but increased renal perfusion pressure in Dahl...


Natriuretic peptides appear to play an important role in preventing the development of arterial and pulmonary hypertension. Overexpression ofthe genes encoding ANP and BNP results in raised circulating concentrations of these peptides and substantially decreased arterial BP (173,174). Moreover, overexpression of ANP protects against the development of pulmonary hypertension in animals exposed to chronic hypoxia. Conversely, ANP gene KO mice are prone to develop salt-sensitive arterial hypertension and pulmonary hypertension with accompanying right ventricular hypertrophy (175). The ability of ANP to defend against salt-induced arterial hypertension may reflect a combination of the natriuretic, diuretic, vasorelaxant, and sympathoinhibitory properties of this peptide. The NPR-A gene KO mice phenotype is also characterized by arterial hypertension, which appears to be independent of sodium loading (176). Genetic disruption of NPR-A is also associated with a marked cardiac hypertrophy...

Diet Hypertension

The major dietary risk factors for hypertension and stroke are as follows 4 Overweight. Obesity is commonly associated with high blood pressure. Overweight hypertensive persons who lose weight often experience a significant reduction in blood pressure.21 intake of essential PUFAs can increase risk of high blood pressure (see Fig. 5.9). 0 Salt. Although for most people sodium in the diet plays only a minor role in determining blood pressure, some individuals are very sensitive to sodium in the diet. Individuals with a family history of hypertension or who are older than 55 years are most likely to be sodium sensitive.22 In about one-third of cases of hypertension, blood pressure can be significantly lowered by limiting sodium intake, most of which comes from salt added to processed foods, such as bread, cheese, canned soups and salty snacks. 0 Potassium. High sodium intake is a much stronger risk factor when combined with low potassium intake.5 People with low intakes of potassium are...

Pharmacological Stress Testing and Noninvasive Imaging

Thirty-nine patients (10.3 ) could not finish the study because of intolerable side effects, which were defined as dysrhythmia and severe hypotension or hypertension. Patients with positive DSE had a sevenfold increased risk of cardiac death, AMI, rehospitalization for unstable angina, or revascularization within 6 mo. In those patients with a negative DSE, one cardiac death was reported (0.3 ) and seven patients underwent revascularizations (2 ). No patients with AMI, however, were observed at 6-mo follow-up (65). Although DSE appears to be an effective means for risk stratification, its cost-effectiveness in the ED setting is not known. It is also important for the institution to have on staff physicians who are interested in DSE and have expertise in this methodology.

Some Common Design Configurations

Some extent by separating treatments with a 'washout' period and, more importantly, by selecting treatment lengths based on a knowledge of the disease and the new medication. The crossover design is best suited for chronic stable diseases e.g. hypertension, chronic stable angina pectoris, where the baseline conditions are attained at the start of each treatment arm. The pharmacokinetic characteristics of the new medication are also important, the principle being that the plasma concentration at the start of the next dosing period is zero and no dynamic effect can be detected.

Atr Gene Polymorphism And Atherosclerosisrelated Diseases

Coronary artery disease (CAD) is a major public health problem in industrialized countries. Dyslipidemia, arterial hypertension, and diabetes mellitus, the main risk factors for CAD apart tobacco consumption, are influenced by both environmental and genetic factors. Several studies have suggested that the activation of the RAS could be an important contributor to CAD. The best-documented of associations between the occurrence of CAD and polymorphisms in genes RAS component is the I D polymorphism of the ACE gene. After the initial work of Cambien et al. (67), who first suggested the potential role of the ACE D allele as an independent risk factor for myocardial infarction (MI), other case-control studies either confirmed or were in disagreement with their findings (68-70). The M235T variant of AG gene has also been associated with MI but, as in hypertension, with ethnic variability (19). A1166C polymorphism in AT1R gene does not seem to be a direct risk factor for CAD or MI, but, in...

Epidemiologic Evidence Supporting Physical Activity

In the United States alone, it has been estimated that roughly 250,000 deaths per year are attributed to lack of regular physical activity3 (roughly one-quarter of all preventable deaths annually). However, others have suggested that these figures may be significantly underestimated.23 Ongoing longitudinal studies have provided consistent evidence of varying strength documenting the protective effects of activity for a number of chronic diseases, including CHD, chronic heart failure (CHF), type 2 diabetes, hypertension, osteoporosis, and site-specific cancers.2,3,6 In contrast, low levels of physical fitness or activity are consistently associated with higher cardiovascular and all-cause mortality rates.2,3,13,14 Midlife increases in physical activity, fitness level, or both, through change in occupation or recreational activities, are associated with a decrease in mortality rates.24,25 Considering the last few years alone (2000-2004), an impressive volume of data has been published...

Conclusions And Perspectives

Hypertension is a polygenic disease, and most probably multiple genes are involved in the etiology of this disease in different ethnic groups. Although initial studies, based on microsatellite markers, had shown that renin, ACE, and angiotensin receptor type 1 genes are not involved in hypertension, recent studies have suggested that certain polymorphic variants of renin and angiotensin receptor may be involved in human essential hypertension (64). It is also important to mention that other genes such as adducin (65), P2-adrenergic receptor (66), and G protein P3 subunit (67) have also been suggested to be involved in human hypertension. It will be important to examine whether interaction of these genes leads to hypertension.

Residual Stress and Strain

Blood vessels are known to retract both longitudinally and circumferentially after excision. This retraction is caused by the relief of distending forces resulting from internal pressure and longitudinal tractions. The magnitude of retraction is influenced by several factors. Among these factors are growth, aging, and hypertension. Circumferential retraction of medium-caliber blood vessels, such as the carotid, iliac, and bracheal arteries, can exceed 70 following reduction of internal blood pressure to zero. In the case of the carotid artery, the amount of longitudinal retraction tends to increase during growth and to decrease in subsequent aging 5 . It would seem reasonable to assume that blood vessels are in a nearly stressfree state when they are fully retracted and free of external loads. This configuration also seems to be a reasonable choice for the reference configuration. However, this ignores residual stress and strain effects that have been the subject of current research...

And Michael R Garrett MS mba

Genetic approaches to identify BP regulatory genes involve the use of rat models with elevated BP (hypertension). Typically, genetic linkage analyses and substitution mapping using congenic strains are performed. These studies are designed to enable the identification of BP regulatory genes primarily by virtue of their location on the rat genome. This chapter captures the current status of studies aimed at identifying BP causative genes using various congenic rat strains. Key Words Hypertension genetic rat animal model QTL cardiovascular renal disease causative genes.

Contraindications to CPX in CHF

Some conditions remain contraindications to exercise testing in CHF very recent myocardial infarction, unstable angina, severe ventricular arrhythmias, symptomatic hypotension, and mobile intracardiac thrombus. Caution is warranted if there is severe pulmonary hypertension, aortic stenosis, or hypertrophic cardiomyopathy, although exercise testing is increasingly being used in these conditions. Left bundle branch block remains a contraindication unless coronarogra-phy is known to be normal. Heart failure per se clearly is no longer a contraindication but CPX has little value when done very recently after an acute decompensation or prolonged bedrest.

Calibration of the System

Analysis of the resting phase is important and already provides some insights. It is necessary to wait 3-4 minutes of resting while gas exchange is measured to ensure stability. Baseline VO2 should be between 3 and 5 mL min kg (but lower values may be found in patients with severe heart failure), the respiratory exchange ratio (RER) below 0.90, and ventilation quiet. Ventilatory oscillations can be observed at this stage this is the consequence of a periodic way of breathing and is always associated with severe circulatory failure and or pulmonary hypertension. The mechanism of this profile is not exactly known but seems to

Individual risk factors

Extensively for possible clinical conditions in which patients are at additional risk for the induction of ARF 122 Swartz et al. 122 using a retrospective analysis of factors related to renal failure following major an-giography, reported that in addition to renal insufficiency, abnormal liver function tests, hypoalbumin-emia, diabetes mellitus and proteinuria all were significantly correlated with the patient group which developed renal failure. They also noted a prevalence of 2.5-risk factors case of contrast-associated nephr-opathy. Cochran et al. 123 used an odds-ratio analysis of 28 clinical factors that might correlate with increased risk for the development of contrast-associated nephropathy. In addition to underlying renal disease and elevated serum creatinine, their data confirmed proteinuria as a risk factor but failed to substantiate diabetes mellitus or abnormal liver function. They did demonstrate that male gender, hypertension, and vascular disease all were associated...

Pathophysiology ofHemodynamic Stress and Cardiac Injury

Acute PE increases pulmonary vascular resistance, partly owing to hypoxic vasoconstriction. In patients without prior cardiopulmonary disease, the mean pulmonary artery pressure can double to approx 40 mmHg. A further doubling of pulmonary artery pressure may occur in patients with chronic thromboembolic pulmonary hypertension (11).

Right ventricular performance

An augmentation of right ventricular preload and positive inotropic stimulation will improve right ventricular performance.99 101 The right ventricle is more sensitive to increases in afterload than the left one. With increasing resistance to ejection (for example, in pulmonary hypertension), the right ventricle readily uses up its preload reserve and dilates. As a result of the high chamber compliance of the thin walled right ventricle, the

Exercise Training in Valvular Heart Disease

Asymptomatic or mildly symptomatic patients with valvular heart disease are usually not included in medically supervised exercise training programs as part of the conservative management. However, physical conditioning and individually tailored exercise training are advisable for most patients after valve replacement, taking into account left ventricular function, previous level of training, the type of valve replaced, pulmonary hypertension, and heart rate. The general circulatory responses to exercise are of benefit to most of these patients, and could contribute to an overall improvement in the quality of life.

Use in Prevention and Therapy

Calcium can reduce blood pressure in hypertensive patients, particularly those who are salt sensitive or who have low plasma levels of renin (the kidney pressor hormone) (Fig. 3.10).1,8,9 Risk of hypertensive disorders of pregnancy (pree-clampsia) may be reduced by ample intake of calcium10. daily supplement of 1500 mg of calcium given to women with hypertension for 4 years produced significant and sustained lowering of systolic blood pressure. In the supplemented group mean systolic press-urefell by 13 mm Hg inthe unsupplemented group it increased by 7 mm Hg.

Targeting Systemic

We generated transgenic mice containing the entire hAGT gene in order to study its tissue- and cell-specific expression and its role in the pathogenesis of hypertension (14). The transgene employed contains all five exons and intervening intron sequences, and extends approx 1.2 kb upstream and 1.4 kb downstream of the gene. The expression pattern of hAGT gene was found to be very consistent with the tissue-specific expression of the mouse and rat AGT genes and with the expected pattern of AGT expression in humans. Consistent with previous reports, analysis of the cellular origin of kidney hAGT in these transgenic mice revealed that it was exclusively localized to the epithelial cells of the proximal convoluted tubules (18). All together, these data demonstrated that the hAGT transgene was appropriately regulated. It also suggests that these transgenic mice represent a valid model for examining the regulation of hAGT gene. We also evaluated whether elements of the human RAS could...

Scientific Foundations

To get diabetes, high blood pressure, heart attacks, and stroke. (Together, high blood pressure, heart attacks, and stroke are called cardiovascular disease.) A person having less than 1 milligram of C-reactive protein per liter of blood (1 mg L) is at low risk for cardiovascular disease. A person with 1 to 3 mg L has average risk. If a person has more than 3 mg L, they have high risk. Smoking, lack of exercise, and being overweight increase C-reactive protein in the blood.

Les Enantiomeres Du Carteolol

Albuterol Sulfate Reaction

Although both are applied topically to the eye, measurable quantities of these drugs are detectable in plasma, so caution must be employed when the patient is also taking cardiovascular agents. Structurally related aminoimidazoline Clonidine (35) is a selective a2-agonist taken orally for treatment of hypertension. The anti-hypertensive actions of clonidine are mediated through stimulation of -adrenoceptors within the CNS, resulting in an overall decrease in peripheral sympathetic tone. Guanabenz (36) and guanfacine (37) are ring-opened analogs of by the same mechanism and employed as centrally acting antihypertensives. Methyldopa (12) is another antihypertensive agent acting as an a,-agonist in the CNS through its metabolite, a-methyl-norepineph-rine (65). Methyldopa the drug is the l-(S)-stereoisomer is decarboxylated to a-methyl-dopamine (64) followed by stereospecific -hydroxylation to the (l.R,2S) stereoisomer of a-methylnorepinephrine (65). This...

Individual substances

Tenamfetamine ('ecstasy', MDMA methylenedioxy-methamphetamine) is structurally related to mescaline as well as to amphetamine. It was originally patented in 1914 as an appetite suppressant and has recently achieved widespread popularity as a dance drug at 'rave' parties (where it is deemed necessary to keep pace with the beat and duration of the music popular names reflect the appearance of the tablets and capsules and include White Dove, White Burger, Red and Black, Denis the Menace). Tenamfetamine stimulates central and peripheral a-and p-adrenoceptors thus the pharmacological effects are compounded by those of physical exertion, dehydration and heat. In susceptible individuals (poor metabolisers who exhibit the CYP450 2D6 polymorphism) a severe and fatal idiosyncratic reaction may occur with fulminant hyperthermia, convulsions, disseminated intravascular coagulation, rhabdomyolysis, and acute renal and hepatic failure. Treatment includes activated charcoal, diazepam for...

Exercise Haemodynamics after Valve Surgery

The hemodynamic improvement after valve surgery depends on preoperative degree of impairment and the valve lesion. In patients with aortic stenosis and impaired left ventricular function preoperatively, hemodynamics improve significantly at rest and during exercise after valve surgery. In contrast, patients after mitral valve replacement have a markedly lower exercise tolerance only 40-60 of patients have normal hemodynamics at rest and only 25 during exercise. In patients with mitral stenosis, pulmonary capillary wedge pressure falls significantly after surgery as well as pulmonary hypertension. The degree of pulmonary hypertension preoperatively and the speed of postoperative regression of pulmonary hypertension is of importance for further management, including exercise training.26-28

Radiopague Indicators Of Physiological Spaces And Processes

Diagram Pulmonary Artery Wedge

Figure 2 Illustration of function deducible from micro-CT imaged anatomic micro-schematic. The upper two panels are of the pulmonary arterial tree of a rat left control and right with monocrotaline-induced pulmonary hypertension. The greatly narrowed lumen diameters (right panel ) translate to changes in arterial resistance that can be computed from the arterial tree branching geometry. The lower panels relate to measurement of myocardial fiber direction as a function of transmural location in the LV heart wall. The left shows a short axis CT image of a rat heart and the labeled panels around it are images of transmural and tangential sections through heart wall computed from the 3D image of the heart. The right-most shows the fiber direction as a function of transmural location. This information allows analysis of regional wall stresses and strains. Source From Ref. 37.

The Impact of Fitness on Cardiovascular Diseases

Physical fitness can be measured easily and exactly, and has been shown to have a negative correlation to coronary heart disease. However, there is also a negative correlation between increasing fitness and risk factors like hypertension and hypercholesterolemia. Intervention by physical training has been shown to reduce these risk factors in studies at the Cooper Clinic in Dallas. If these confounders are corrected for, physical inactivity doubles the risk of coronary disease. In highly trained Norwegian skiers, a risk reduction of 4.8 was found compared to the least fit group in the study. In the same study, the quar-tile with the highest fitness had a relative risk of cardiovascular death of 0.4 compared to the quar-tile with poorest fitness.5 Large studies from the US also show a double risk in persons with low exercise capacity compared to those with a high exercise capacity.6 Still it may be questioned whether the training or the high fitness per se is protective. This is...

Facilitated Oxygen Transport And Vasoconstriction

The rates of oxygen transport in the artificial capillary apparatus described above (see Figure 5.1) showed a direct correlation with the mean arterial blood pressure in rats in response to exchange transfusion with the hemoglobins studied (McCarthy et al., 2001). Both aa-Hb and HbA0, which gave higher calculated values for the diffusion transport parameter compared to RBCs and PEG-Hb, exhibited hypertension in the rat model, while the PEG-Hb did not.

Answers To Case 17 Calcium Disorders

Summary This is a 58-year-old female with a history of recurrent nephrolithiasis, presenting for follow-up and found to have calcium oxalate stones. She had an initial serum calcium level that was elevated, as was the repeat serum calcium 1 week later. At the time of her follow up. she was completely asymptomatic. She takes no medications, and has a family history only significant for hypertension.

Dietary Fatty Acids and Sodium Intake Cytokines LVH and CHF

Whereas male gender, obesity, heredity, and insulin resistance may explain some of the variance in LVH, hypertension (HBP) is generally regarded as the primary culprit. Thus, the risks associated with LVH and HBP are intimately linked. Recent data also suggested that low dietary intake of polyun-saturated fatty acids and high intake of saturated fatty acids, as well as HBP and obesity, at age 50 predicted the prevalence of LVH 20 years later. Although the source of saturated fatty acids is usually animal fat, the source of unsaturated fatty acids in that specific Scandinavian population and at that time was less clear and there was no adjustment for other potential dietary confounders such

Clinical Evaluation of Renal Function

27 Fliser D, Ritz E, Mutschler E, Block S, Joest M, Franek E 1997 Renal function in the elderly impact of hypertension and cardiac function. Kidney Int 51 1196-1204 47 Toto RD, Agodoa L, Olutade B, Campese V, Wright J Appel L, Jones C, Coresh J Kirk KA 1997 Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. J Am Soc Nephrol 8 279-287

Objectives in the Management of Individuals with MetS

Patients with MetS have a 1.5- to 3-fold increase in the risk of coronary heart disease and stroke.3 The NCEP ATP III guidelines emphasize the importance of treating patients with MetS to prevent CVD.14 The association between MetS and CVD raises important questions about the underlying pathological process(es), especially for designing targeted therapeutic interventions. Cardiovascular risk reduction in individuals with MetS should include at least three levels of intervention (1) control of obesity and lack of physical activity (2) control of insulin resistance and (3) control of the individual components of MetS, especially hypertension and atherogenic

Effects of Weight Loss on MetS Components

Effective for long-term weight loss are reduced-energy diets, consisting of a 500- to 1000-calorie day reduction. A realistic goal for weight reduction is to reduce body weight by 7-10 over a period of 6 to 12 months. Numerous studies have shown that significant improvement of several abnormalities of MetS, including dyslipidemia, hyperglycemia, and hypertension, can be observed, even with a modest amount of weight loss.6,10 For every kilogram of weight loss the following favorable changes occur fasting serum cholesterol, -1.0 LDL cholesterol, -0.7 triglycerides,-1.9 HDL cholesterol, +0.2 systolic blood pressure, -0.5 diastolic blood pressure, -0.4 and fasting glucose, -0.2 mmol L. The impact of weight reduction on diabetes mellitus is particularly impressive.10

Abducens Pareses Caused by Lesions in the Subarachnoid Space and at the Petrous Apex

The sixth nerve is fixed in position at its exit site from the brainstem, located at the inferior border of the pons, and at its entry into the dura of the clivus. Caudal displacement of the brainstem can result in bilateral traction injuries of the sixth nerves as a nonspecific sign of a distantly located, space-occupying disease (supratentorial masses, hemorrhages, or edema, variations in intracranial pressure following lumbar puncture, and idiopathic intracranial hypertension IIH ). While still in the subarachnoid space or shortly after its entry into the dura, the sixth nerve passes in close proximity to the apex of the petrous bone, the facial nerve, and the trigeminal nerve. Paramastoid inflammatory disease and tumors of the petrous apex produce Grad-enigo syndrome, a sixth nerve palsy accompanied by a deep, boring pain that radiates to the brow and temples. Nasopharyngeal carcinomas that have eaten through the clivus can produce an identical set of symptoms. They can also...

Myeloproliferative Symptoms

Increases in circulating mature (i.e., neutrophils) and immature (i.e., myelocytes, metamyelocytes, myeloblasts, etc.) myeloid cells occur in varying degrees in MMM. These cells have a propensity for accumulation in the reticuloendothelial system, particularly in the spleen and liver.8 These organs expand to accommodate the burden of myeloid cells, and the resulting hepatosplenomegaly may lead to pain, early satiety, sequestration of erythrocytes and platelets, and portal hypertension.9 Extramedullary hematopoiesis also can occur in the lungs (leading to pulmonary hypertension10), abdomen, spine,11 and pericardium.12

What Does the Patient Have Medical and Nutritional Status

The question What does the patient have includes medical diagnosis and risk stratification, type of metabolic abnormality (dyslipi-demia, diabetes, overweight) and the associated risk factors which may have an influence on the dietary counseling (smoking, hypertension, sedentariness).

Acquired Isolated Unilateral Trochlear Pareses

Trochlear palsies of this sort in most cases must be attributed to a microvascular pathogenesis. This is consistent with their abrupt onset and their associated risk factors, such as diabetes mellitus, age of 50 or more, hypertension, and generalized arteriosclerosis. In most cases, the cause cannot be proven. A general medical exam to look for unsuspected hypertension or threshold diabetic states is indicated. Usually the problem resolves spontaneously within about 3 months. If it does not recover or is joined by additional signs and symptoms, a more thorough investigation is needed, and should include an MRI of the brain and a lumbar puncture.

The pulmonary circulation

The mechanisms affecting the distribution of blood flow in the normal lung will be considered first. This will be followed by a discussion on the effects of posture, haemorrhage, mechanical ventilation, and lung disease. The methods of studying the pulmonary circulation will then be outlined, followed by a brief review of the way in which anaesthetic and related drugs may alter the distribution of blood flow, and so affect the efficiency of gas exchange. Finally, we shall consider the problem of pulmonary hypertension, the effects produced by pulmonary vasodilator drugs, and the pathophysiology of pulmonary oedema.

Who Benefits from Guidelines

Industry heavily underwrites guideline creation, at least in nephrology. Amgen is the principle sponsor of the NKF-K DOQI guidelines, and as Coyne points out (op. cit.), with potential financial benefits from guidelines for anemia and bone management. There are many other examples. The entire guideline process is tilted towards increasing use of pharmaceuticals since most clinical trials are sponsored drug studies (funded by industry). It is easy to see how guidelines recommending ever-lower blood pressure, cholesterol and glycosylated hemoglobin targets could fuel a major expansion of drug prescribing in these areas.

Methods using the distribution of flow as an index of pulmonary vascular tone

It is obvious that the conditions outlined above severely limit the number of useful observations that can be made. Furthermore, as the normal vascular bed has very little tone, the action of pulmonary vasodilator drugs can only be studied after constriction has been induced by some other agent (such as hypoxia). Obviously, vasodilator drugs must also be studied in the patients in whom they are likely to be used, but such studies often produce variable results owing to differences in the aetiology of the pulmonary hypertension in each patient. For these reasons we will first consider the actions of drugs on the normal pulmonary circulation and on hypoxic pulmonary vasoconstriction. In the last section we shall consider the problem of pulmonary hypertension and the effects of vasodilator drugs.

And the Cardiovascular System

A wide variety of cardiovascular pathologies are potentially amenable to treatment using gene therapy. Examples include myocardial ischemia, vein graft failure, atherosclerosis, hypercholesterolemia, peripheral ischemia, and hypertension. Gene transfer offers the potential for overexpression of candidate therapeutic genes in these conditions, with the ultimate aim of prevention, improvement, or regression of the condition. Gene therapy has two distinct modes of use. In monogenic disorders, in which a single mutated or absent gene has been identified as being causal, the aim of gene therapy would be to insert the corrected form of the gene into the appropriate target cell type to restore normal function. A number of monogenic cardiovascular diseases have been well documented, for example, in conditions such as hypertension (1) or hypercholesterolemia (2). However, the majority of cardiovascular conditions are complex, polygenic disorders, in which environmental factors, such as diet,...

Congestive Heart Failure

Natriuretic peptides have beneficial actions in heart failure. The natriuretic, diuretic, and vasodilatory effects tend to decrease cardiac preload and afterload. In addition, inhibition of the renin-angiotensin system and SNS will act synergistically with the direct hemodynamic and renal effects. The significance ofthe inhibitory actions ofthe natriuretic peptide system on the renin-angiotensin system is illustrated by the effect of NPR-A blockade. In a canine experimental model ofearly LV dysfunction, NPR-A blockade with the receptor antagonist HS-142-1 resulted in sodium retention, augmented renin release, increased aldosterone production, and accelerated progression to overt heart failure (148, 164). Bilateral atrial appendectomies had a similar effect (164). In an experimental model of canine heart failure, coinfusion of BNP and furosemide resulted in a more profound diuretic and natriuretic response than furosemide alone (165). Moreover, during coinfusion, glomerular filtration...

HsCRP Metabolic Syndrome and Type 2 Diabetes Mellitus

Hdl Metabolic

Clinical practice, such as elevated triglycerides, low HDL-C, obesity, high fasting glucose, and high blood pressure (BP). In the Women's Health Study, e.g., after adjustment for multiple potential confounders, the RRs of incident hypertension for increasing hsCRP quintiles were 1.00 (referent), 1.07 (95 CI 0.95-1.20), 1.17 (95 CI 1.04-1.31), 1.30 (95 CI 1.17-1.45), and 1.52 (95 CI 1.36-1.69), respectively (p for trend of

Guide To Further Reading

Anderson IM, Nutt D J et al 2000 Evidence-based guidelines for treating depressive disorders with antidepressants a revision of the 1993 British Association for Psychopharmacology guidelines. Journal of Psychopharmacology 14 3-20 Ballenger J C et al 1998 Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 59 47-54 Ballenger J C et al 1998 Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 59 54-60 Ballenger J C et al 2000 Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. Journal of Clinical Psychiatry 61 60-66 Ballenger J C et al 2001 Consensus statement on generalized anxiety disorder. Journal of Clinical Psychiatry 62 53-58 Davies S J C et al 1999 Association of panic disorder and panic attacks with hypertension. American Journal of Medicine...

Causes Of Hyponatremia

5.3 An 83-year-old woman comes to your office complaining of a headache and mild confusion. Her only medical history is remarkable only for hypertension, which is well controlled with hydrochlorothiazide. Her examination and laboratory tests show no signs of infection, but her serum sodium level is 119 mEq L, and plasma osmolarity is 245 mOsm kg. She appears to be clinically hypovolemic. What is the best initial therapy

Regulation of the cardiovascular system

The physical characteristics of the vascular system are dynamic and more complex than previously realised. Age and certain pathophysiological conditions, such as hypertension, diabetes, and atherosclerosis, result in a progressive stiffening of the conduit (large artery) vessels related to intimal and smooth muscle changes. Vascular smooth muscle hypertrophy as a primary or a secondary phenomenon results in a hypersensitivity to control mechanisms. In any discussion pertaining to cardiovascular regulatory mechanisms, pathophysiological changes must be considered. Interestingly, ventricular hypertrophy may proceed with elevated or normal blood pressure. This appears to be related to the very important pulsatile component of ventricular load, which is not necessarily captured by measurements of blood pressure.1 An understanding of the differential impact of conduit and resistance vessels will expand future investigations into cardiovascular control mechanisms as well as pharmocotherapy.

Recommendations Regarding Use of BNP for Screening

At this time, there is insufficient evidence to support BNP testing for screening asymptomatic, low-risk populations for LV systolic dysfunction. There may be some role for BNP to screen high-risk subgroups such as patients with prior myocardial infarction, patients with diabetes, or those with an extended history of uncontrolled hypertension. However, echocardiography is likely to remain the primary method of assessing LV function in this setting. Figure 11 depicts one possible algorithm for BNP testing in the outpatient setting (55). This algorithm is framed around a lower cut point of 20 pg mL and an intermediate cut point of 40 pg mL. Patients with values above the cut points of 20 and 40 pg mL should be referred for echocardiography with consideration of evaluation by a cardiovascular specialist. Fig. 11. Algorithm for using BNP in primary care setting. (Adapted from ref. 50.) HF, heart failure CAD, coronary artery disease DM, diabetes mellitus HTN, hypertension CXR, chest X-ray...

Scope of Problem and Risks

Hypertension is the most common primary diagnosis at physician office visits in the United States each year. Approximately 50 million Americans have hypertension and approximately 30 are unaware of their problem. The prevalence is higher in African-Americans and in older patients. National Health and Nutritional Examination Surveys (NHANES) data suggest that hypertension is responsible for approximately one-third of heart attacks, one-half of heart failure, and one-fourth of premature deaths. Most patients with end-stage kidney disease are hypertensive. Hypertensive nephrosclerosis is responsible for approximately one-fourth of end-stage kidney disease. The risk of complications is directly related to the elevation of the blood pressure the higher the blood pressure, the higher the risk.

Prediabetes And Metabolic Syndrome

The American Diabetes Association recommends screening for prediabetes for individuals who are 45 years old or older and have a BMI that suggests obesity (BMI 25 kg m2). Screening is also suggested for individuals who are less than 45 years old but obese and have other risk factors, such as family history of diabetes, or ethnicity that is associated with diabetes or hypertension. For individuals who meet the requirements for screening, screening should be repeated every 3 years.19

Renal Protection By Tissue Kallikrein And Kinin

The link between renal function and the KKS has been demonstrated by several studies. Renal kallikrein excretion has been reported to be significantly reduced in patients with mild renal disease, and more markedly reduced in patients with severe renal failure (66,67). Genetic linkage analysis has shown that a polymorphic site in the proximal promoter region of the human tissue kallikrein gene is associated with the development of end-stage renal disease and hypertension (68,69). Additionally, the kallikrein promoter polymorphism participates in regulating gene expression and modifies blood pressure in response to dietary salt intake (70). These findings suggest that expression of the kallikrein gene may serve as a powerful marker for linkage analysis in populations with salt-sensitive hypertension and renal disease. A variety of studies, including our own, indicate a direct protective effect of the KKS in the kidney. A previous report by other investigators showed that intravenous...

Inhibition Of Synthesis Of Transmitter

Metirosine (a-methyl-p-tyrosine) is a competitive inhibitor of the enzyme tyrosine hydroxylase, which converts tyrosine to dopa as dopa is further converted to noradrenaline and adrenaline they are similarly depleted by metirosine. It is used as an adjuvant (with phenoxybenzamine) to treat phaeo-chromocytomas that cannot be removed surgically. Catecholamine synthesis is reduced by up to 80 over 3 days. It also readily penetrates the CNS and depletes brain noradrenaline and dopamine causing reserpine-like side effects (see above). Hence, in patients whose life expectancy is threatened more by tumour invasion than by mild or moderate hypertension, the need for the drug should be weighed carefully.

Autonomic ganglionblocking drugs

Hexamethonium was the first orally active drug to treat hypertension. Like all agents in this group it blocks sympathetic and parasympathetic systems alike. Severe side effects have rendered them of historical interest only in hypertension therapy.23 Trimetaphan, a short-acting agent (given by i.v. infusion, initially at 3-4 mg min), also has direct vasodilator effect it is used for producing hypotension to provide a blood-free field during surgery, and can be used for emergency control of hypertension pressure may be adjusted by tilting the body it provides 'minute-to-minute' control, when the lack of selectivity is important.

Central nervous system

Clonidine (Catapres) is an imidazoline which is an agonist to a2-adrenoceptors (postsynaptic) in the brain, stimulation of which suppresses sympathetic outflow and reduces blood pressure. At high doses it also activates peripheral a2-adrenoceptors (presynaptic autoreceptors) on the adrenergic nerve ending these mediate negative feedback suppression of noradrenaline release. In overdose clonidine can stimulate peripheral a -adrenoceptors (postsynaptic) and thus cause hypertension by vasoconstriction. Clonidine was discovered to be hypotensive, not by the pharmacologists who tested it in the laboratory but by a physician who used it on himself as nose drops for a common cold.24 The is 6 h. Clonidine reduces blood pressure with little postural or exercise related drop. Its most serious handicap is that abrupt or even gradual withdrawal causes rebound hypertension. This is characterised by plasma catecholamine concentrations as high as those seen in hypertensive attacks of...

Tissue Kallikrein Protects Against Saltinduced Renal Injury

Progressive renal injury is the consequence of a process of destructive fibrosis. High salt intake induces hypertension, cardiac hypertrophy, and progressive renal damage. DSS rats represent a model of progressive and sclerotic renal lesions and have been regarded as the closest model of human salt-sensitive hypertension. After high salt intake, DSS rats develop hypertension, severe renal damage, cerebral infarction, and hemorrhage (38,72,74). An increase in apoptosis in the glomerular and tubular compartments has also been observed in DSS rats (75). This event occurred at a time when renal function was markedly impaired and irreversible changes in renal morphology had developed, indicating a pathological role for apoptosis in renal dysfunction and fibrosis. We have shown that kallikrein gene transfer reduced salt-induced hypertension, glomerular sclerosis, and tubulointerstitial damage in DSS rats (38,72). In addition, we recently demonstrated that kallikrein gene delivery in DSS...

Causes Of Atrial Fibrillation

Ondas Delta

Many patients with AF cannot be cardioverted and expect to remain in sinus rhythm. Two important prognostic factors are left atrial dilation (atrial diameter 4.5 cm predicts failure of cardioversion) and duration of AF. The longer the patient is in fibrillation, the more likely the patient is to stay there ( atrial fibrillation begets atrial fibrillation ) as a consequence of electrical remodeling of the heart. In patients with chronic AF, the management goals are rate control, using drugs to reduce AV nodal conduction as described earlier, and anticoagulation. Patients with chronic AF who are not anticoagulated have a 5 per year incidence of clinically evident embolization such as stroke. For chronic AF caused by valvular disease such as mitral stenosis, the annual risk of stroke is substantially higher. Warfarin anticoagulation reduces the risk of stroke in patients with chronic AF by two thirds. Warfarin does not produce a predictable dose-related response therefore, the level of...

Kallikrein Gene Delivery Protects Against Pressurebased Stroke

Hypertension is critical in the development of stroke in humans. In stroke-prone, spontaneously hypertensive rats (SHRSP), high salt intake accelerates the development of malignant hypertension (79). In the brains of SHRSP, fibrinoid necrosis and associated thrombosis primarily affect cerebral arterioles, leading to their obstruction and infarction, whereas cerebral hemorrhage is caused by microaneurysms (80). In addition, a lethal form of hypertension has been shown to develop in DSS rats fed a high-salt diet at an early age (81). Pathological changes in the brain of DSS rats affected by stroke include hemorrhage, edema, and infarction. We showed that a single injection of adenovirus carrying the human tissue kallikrein gene significantly reduced hypertension, stroke-induced mortality, aortic hypertrophy, and cerebral hemorrhage in DSS rats on a highsalt diet (74). These findings indicate that kallikrein kinin may play a protective role in pressure-based stroke.

Threshold Andtargets For Treatment

The British Hypertension Society guidelines30 require that antihypertensive drug therapy be initiated The optimal target is to lower BP to or below 140 85 mmHg in nondiabetics and 140 80 mmHg in diabetics. The World Health Organization International Society for Hypertension sets a more rigorous target of 130 85 mmHg. Effective treatment reduces the risk of all complications strokes and myocardial infarction, but also heart failure, renal failure, and possibly dementia. It is easier in individual trials to demonstrate the benefits of treatment in preventing stroke, because the curve relating risk of stroke to blood pressure is almost twice as steep as that for myocardial infarction. What this tells us is not that the relative risk of myocardial infarction due to hypertension is irreversible but that substantial reduction in the absolute risk of myocardial infarction needs attention to hypercholesterolaemia as well as hypertension.31 30 The British Hypertension Society Guidelines are...

Adrenergic Neuron Blocking Drugs

Adrenergic neuron blocking drugs are selectively taken up into adrenergic nerve endings by the active, energy-requiring, saturable amine (noradrenaline) pump mechanism (uptake-1). They accumulate in the noradrenaline storage vesicles from which they are released in response to nerve impulses, diminishing the release of noradrenaline and so all sympathetic function. They do not adequately control supine blood pressure and are prone to interactions with other drugs affecting adrenergic function, e.g. tricyclic antidepressants and topical nasal decongestants. They are virtually obsolete in hypertension. Reserpine is an alkaloid from plants of the genus Rauivolfia, used in medicine since ancient times in southern Asia, particularly for insanity more recently, reserpine was extensively used in psychiatry but is now obsolete. Reserpine depletes adrenergic nerves of noradrenaline primarily by blocking amine storage within vesicles present in the nerve ending, so reducing stores of releasable...

Sexual function and cardiovascular drugs

All drugs that interfere with sympathetic autonomic activity, including diuretics, can potentially interfere with male sexual function, expressed as a failure of ejaculation or difficulty in sustaining an erection. Nevertheless, placebo-controlled trials have emphasised how common a symptom this is in the untreated male population (approaching sometimes 20-30 ). It is also likely that hypertension itself is associated with an increased risk of sexual dysfunction since loss of NO production by the vascular endothelium is an early feature of the pathophysiology of this disease. Laying the blame on antihypertensive medication is probably

Sexual Intercourse Andthe Cardiovascular System

Such changes in the healthy may reasonably be thought to bode ill for the unhealthy (with hypertension, angina pectoris, post myocardial infarction). Sudden deaths do occur during or shortly after sexual intercourse (ventricular fibrillation or subarachnoid haemorrhage), usually in clandestine circumstances such as the bordello or the mistress's boudoir, or when the relationship is between an older man and a younger woman although this may just reflect reporting bias in the press. In one series, 0.6 of all sudden deaths were (reportedly) attributable to sexual intercourse and in about half of these cardiac disease was present. Clearly it is undesirable that the older patient with coronary heart disease should aspire to the haemodynamic heights attainable in youth. If there is substantial concern about cardiovascular stress (hypertension or arrhythmia) during sexual intercourse in either sex, a dose of labetalol about 2 hours before the event may well be justified (taking account of...

Multiple Roles Of Kallikreinkinin In Cardiovascular And Renal Disease And Stroke

Using transgenic and somatic gene transfer approaches to achieve a continuous supply of kallikrein kinin in vivo, we have shown that the KKS exhibits protective effects in hypertension and cardiovascular, renal, and central nervous systems. Our studies demonstrated that kallikrein gene delivery exhibits multiple beneficial effects in the heart, kidney, blood vessel, and brain in various animal models (Fig. 3). These include blood

Aortic Aneurysm Dissections Ruptures

Classification Aortic Dissection

Etiologies of acute aortic dissection include Marfan's syndrome, cystic medial necrosis, and hypertension. The presence of a bicuspid aortic valve has a high coincidence with aortic dissection. Acute aortic dissection arises from separation of the aorta within the media. The media and adventitia of the aorta literally dissect away from the intima and the inner portion of the media. Controlling the patient's hypertension is essential in slowing or halting the progression of the aortic dissection. There is always an intimal tear associated with the aortic dissection which permits blood to dissect into the media, and the location of this intimal tear is critical for planning surgical management. The tear is propagated simply by the pulsatile effect of cardiac contraction. Although the progression of the aortic dissection varies, usual locations are the right anterior portion of the ascending aorta, greater curvature of the transverse arch, and left anterolateral wall of the descending...

Biopsy Techniques Patient Selection and Tissue Handling

Second trimester of pregnancy for proteinuria with or without hematuria, hypertension, renal insufficiency, and nephrotic syndrome. Adequate tissue was obtained with a percutaneous method in all but 3 cases on initial biopsy attempts. One patient developed hemorrhage 4 days after biopsy while receiving therapy with plasma exchange. Otherwise there were no serious complications. Patients in the ICU receiving mechanical ventilatory assistance with pulmonary-renal syndromes pose a special technical challenge. Seven such patients underwent percutaneous biopsy using ultrasound guidance. Adequate tissue was obtained in all. None had gross hematuria, although 2 patients did receive blood transfusions however, both had been previously transfusion dependent. Some authors have advocated the use of CT guidance in particularly obese patients in whom ultrasound localization is difficult because of poor resolution of the kidneys. Percutaneous biopsy has been shown to be safe and effective in series...

Mechanisms of Malnutrition in Chronic Pancreatitis

Chronic Pancreatitis Mechanism

Moreover, abdominal pain induced by food ingestion is common in these patients and results in decreased oral intake leading to weight loss. Inadequate food intake owing to recurrent or near continuous pain usually accounts for the initial 10-20 loss of body weight. However, the patho-physiology of this abdominal pain is poorly understood. Pancreatic hypertension, elevated interstitial fluid pressure, pancreatic ischaemia, damage to pancreatic nerves, tissue necrosis, pseudocyst formation, and common bile duct and or duodenal obstruction may cause the abdominal pain 84 .

Disorders with Hypokalemia and a Normal or High ECF Volume

Treatment For Hyperkalemia

- Clinical Picture This diagnosis should be suspected in patients with hypertension and unexplained hypokalemia with renal K+ wasting. Nevertheless, hy-pokalemia is not a universal finding in these patients 69 . - Differential Diagnosis The finding of very low plasma renin activity (PRA) with high plasma aldosterone levels separate patients with primary hyperal-dosteronism from those with other causes of hypertension and hypokalemia (Figure 15, Tables 3 and 4). Patients with glucocorticoid remediable aldosteronism (GRA), however, also have elevated plasma aldosterone levels with suppressed PRA. These patients typically have the onset of hypertension in early adulthood and a strong family history of hypertension, cardiovascular, and cerebrovascular events. The hypersecretion of aldostero-ne in these patients is suppressed with the - Clinical picture The onset of severe hypertension may occur in early adulthood. There is often a strong family history of hypertension and early onset of...

Licorice Glycyrrhizin

One trial (20), which evaluated a glycyrrhizin-based compound against other herbs, included 193 hepatitis C patients, followed prospectively for 2-16 yr for evidence of progression to cirrhosis or the development of hepatocellular carcinoma. Although glycyrrhizin appeared to slow the histological progression of the disease, both groups appeared to progress to carcinoma more frequently than in similar patients treated with IFN. Side effects attributed to glycyrrhizin included hypokalemia in 11 and hypertension (HT) in 3.6 . In a single randomized control study of iv glycyrrhizin vs placebo, among 58 IFN nonresponders or patients unlikely to respond (cirrhotic patients with genotype 1), the herb resulted in lower ALT, with no effect on HCV RNA levels (21). The adverse effects of glycyrrhizin in humans are well-characterized. Glycyrrhizin inhibits 11- -hydroxysteroid hydrogenase in the kidney, inhibiting the conversion of cortisol to cortisone. This results in a...

Inflammation and atherothrombosis

There is extensive literature supporting the role of inflammation in CAD. Hemodynamic forces from hypertension and oxidative stressors, such as tobacco and hyperglycemia, result in vascular endothelial injury. The attachment of leukocytes, transformation of monocytes into macrophages, and subsequent uptake of cholesterol lipoproteins initiate the fatty streak. Cytokine release from the fatty streak recruits further inflammatory cells (macrophages, mast cells, activated T cells), with resulting uptake and oxidation of low-density lipoprotein (LDL). These cytokines also stimulate smooth muscle cell proliferation and development of a collagenous fibrous cap that covers this inflammatory mixture to form the mature atherosclerotic plaque 2 .

Clinical Evaluation Of Tetrameric Hemoglobin In Trauma

Equal to the increase in oxygen-carrying capacity crystalloid or colloid solutions provided equally rapid correction of the elevated whole blood lactate'. In a follow-up study (Poli de Figueiredo et al., 1997), the infusion of low-dose (4 ml kg 14 g Hb) DCLHb into swine subjected to hemorrhagic shock prompted the authors to further warn that 'pulmonary hypertension and low peripheral perfusion may offset benefits for trauma patients'. Although the authors of the DCLHb trial cited several animal models that appeared to support their study hypothesis, none of these models replicated their study design - a lesson for future conduct of clinical trials with HBOCs.

Philosophies Of Gene Therapy

Gene therapy promises to be the next frontier for treatment of and possibly a cure for complex diseases like hypertension. A variety of studies over the past few years have looked at different gene targets and gene delivery vectors as strategies. Currently, therapeutic agents are chosen by targeting the genes that are important in BP regulation. Whereas this technique should yield promising antihypertensive results, ideal gene targets would be those that have not only been implicated in hypertension, but also have been implicated in some of the target organ damage that is associated with hypertensive disease, such as the heart, kidney, vessels, etc. Over the last several years, our lab has mainly focused on the genetically manipulated renin-angiotensin system (RAS). This system has long been associated with hypertension. The RAS is essential in both the normal regulation of BP, as well as in the pathophysiology of hypertension. This system is also involved in, but not limited to, the...

Coronary flow reserve

Tachycardia And Increased Contractility

Hypertension will, however, preserve CRF (R3, Fig 4.10). Fig 4.10 Diagram of pressure-flow relationships during autoregulation in the normal (A1) and in the left ventricle with anaemia or increased contractility or hypertrophy (A2). As pressure-flow relationships during maximal vasodilation remain about the same (D), coronary vascular reserve will be lower in the abnormal (R2) than in the normal (R1) left ventricle. Elevation of coronary perfusion pressure (as in hypertension) may restore or even increase absolute coronary vascular reserve (R3). (Reproduced with permission from Hoffman JIE. Maximal coronary flow and the concept of coronary vascular reserve. Circulation 1984 70 153-9.)

Periodontal Disease And Pregnancy Outcome

Pregnancy And Periodontitis Pictures

The primary cause of LBW infant deliveries is preterm labor or premature rupture of membranes. Factors such as smoking, alcohol or drug use during pregnancy, inadequate prenatal care, race, low socioeconomic status, hypertension, high or low maternal age, diabetes, and genitourinary tract infections increase the risk of preterm LBW. However, these risk factors are not present in approximately one fourth of preterm LBW cases, leading to a continued search for other

Signs and Symptoms of Nonarteritic Anterior Ischemic Optic Neuropathy

The average age of patients with acute nonarteritic anterior ischemic optic neuropathy (NAION) is about 61 years. The visual loss occurs abruptly and without a prodromal warning, usually while the patient is asleep or within a 12-h period, and there is no associated pain or headache. The initial swelling of the optic disc subsides within 2 months, leaving a pale, atrophic appearance, which is often sectoral (most commonly located in the superior half of the disc). There is for the most part no or very little recovery of function. In about 10 to 20 of cases, there is one or more additional episodes of abrupt loss, in a descending staircase pattern, within the ensuing 2- to 3-week period after the acute onset. Later recurrences of loss in the same eye are very uncommon, but involvement of the contralateral eye can generally be expected within the subsequent 5-year period. As in other ischemic disorders, several risk factors play a role in the process. Aside from the association with...

Cardiac Complications Of Therapy

Cardiovascular mortality is the third main cause of death in patients with HL, after deaths due to HL and secondary malignancies. The relative risk of cardiac death is greatest in irradiated children and adolescents but the absolute risk increases with age at the time of irradiation. Cardiovascular deaths are mainly due to coronary artery disease accelerated by radiotherapy. Increased risks of cardiac events are particularly observed in patients who have known cardiac risk factors such as hypertension and hyperlipidemia. The addition of chemotherapy to radiation treatment does not appear to increase the coronary disease risk. Other late cardiac toxicities of radiation and chemotherapy include peri-cardial disease, cardiomyopathy, valvular defects, and conduction abnormalities.

Arterial blood pressure

During incremental exercise, systolic blood pressure (SBP) increases 7-10 mmHg for every 0.2 L-min-1 increment of Vo2, achieving an increase above resting of 50-70 mmHg at peak exercise. In contrast, diastolic blood pressure (DBP) tends to decrease slightly with exercise, by 4-8 mmHg 62, 63 . Criteria for exercise hypertension have been defined in many different ways but an exaggerated SBP response to exercise has been most consistently used and is likely to be the most reliable and reproducible criterion 64 . The Framingham Heart Study considered males with a SBP 210 mmHg and females with a SBP 190 mmHg at peak exercise as having a hypertensive response 65 . Isolated exercise hypertension is a risk factor for major cardiovascular event and new resting hypertension 66-68 . Blood pressure normally falls rapidly following the cessation of symptom-limited exercise. Elevated SBP and DBP at 3-min post-exercise have been associated with an increased risk of resting hypertension 69 .

Reflex control of the circulation

Baroreceptor Reflex Arc

Arterial baroreceptors respond most effectively to the rate of change of arterial pressure. The response is greatest to changes of arterial pressure in the physiological range (80-150 mm Hg). Several subcategories of baroreceptors exist that respond to different pressure ranges. Arterial baroreceptors respond more actively to declines in arterial pressure than increases. Evidence suggests that the carotid baroreceptors are more sensitive to pressure changes than the aortic baroreceptors and operate at lower ranges of arterial pressure. Experimental investigations have determined that arterial baroreceptors primarily influence reflex control of cardiac rate and contractility. Control of systemic vascular resistance is of secondary importance. The vessels most influenced by arterial baroreceptors are splanchnic arterioles and venules, with the venules being important in increasing venous return to the heart during the pressor reflex. Evidence also suggests that the arterial...

Prognostic Role of BNP and NTproBNP Across Spectrum of ACS

Nstemi Troponin Bnp

A substudy ofthe Orbofiban in Patients with Unstable Coronary Syndromes-Thrombo-lysis in Myocardial Infarction 16 (OPUS-TIMI 16) trial was among the first to evaluate the prognostic capabilities of BNP in a large population of patients across the entire spectrum of ACS (45). In this study, BNP was measured in 2525 patients at a mean of 40 h after presenting with STEMI, NSTEMI, or unstable angina. BNP levels on admission correlated with age, male gender, white race, hypertension, CHF, peripheral vascular disease, hypercholesterolemia, and smoking status. In addition, elevated levels of BNP were associated with Killip class 1, electrocardiogram (ECG) changes, elevated creatine kinase-MB, and chronic kidney disease. A plasma concentration of BNP 80 pg mL was a powerful

Intravenous Pyelography IVP

Major indications for IVP include acute renal colic and nonglomerular hematuria. In these conditions, IVP is more sensitive than ultrasonography because it provides anatomic definition of the entire urinary tract as well as functional information. Other clinical indications for IVP include renal stone disease, voiding difficulties, neurogenic bladder, recurrent urinary tract infections (UTIs), sterile pyuria, congenital abnormalities (Figure 4), unexplained abdominal pain, and postoperative complications (Table 7). With the advent of ultrasonography, computed tomography (CT), and nuclear imaging, IVP is no longer the first-line diagnostic study in patients suspected of having renal neoplasias, obstructive uropathy, or renovascular hypertension or in the follow-up of renal allograft recipients.

Delivery Methods For Gene Therapy

In hypertension, whether using an AS approach to express reduction or AS mRNA to inhibit an overexpressed protein, or using an induction or sense approach to increase the synthesis of proteins critical to the pathogenesis of the disease, one generally has to transduce somatic cells of the body. Therefore, methodologies for efficient gene transfer are paramount for successful gene therapy. Other essential components of successful gene therapy are the ability to appropriately express the gene, to have long-term survival of the transduced cell(s), and to be able to control expression of the particular gene. There have been several vehicles explored for somatic gene delivery for hypertension, such as naked DNA, liposomes, receptor-mediated delivery, and viral delivery. This last method can be further divided by the type of virus utilized retroviral, adenoviral, adeno-associ-ated, or lentivirus. Each system has certain advantages and disadvantages, which influence their selection. The...

Diaspirin crosslinked hemoglobin DCLHb in cardiac surgery

All patients experienced at least one adverse event (Lamy et al., 2000). Serious adverse events were more frequent in the DCLHb group (50 vs 26 events), and more patients were affected (33 vs 21). The prevalence of the following adverse events was higher in the DCLHb group hypertension, jaundice, increased liver and pancreatic enzymes, and hematuria hemoglobinuria. Postoperative hemoglobin concentration was similar in both groups. Hemodynamically, DCLHb-treated patients tended to have higher systemic and pulmonary pressures and resistances and a lower cardiac output than patients treated with allo-geneic RBCs. In the first phase II study, with 60 patients, the amount of RBCs transfused was less in hemoglobin raffimer-treated patients, but the percentage of patients completely avoiding allogeneic RBC transfusions was similar in both groups (Hill et al., 2002b). The incidence of hypertension was higher and there was a greater postoperative increase in certain liver enzymes and lipase in...

Extracellular Matrix

Extracellular Matrix Stain

In addition to the various morphologic characteristics of allograft valves, a variety of gender and age-related anatomic and histologic changes occur in human aortic valves. The following changes are most frequently observed in valves harvested from male donors 1) degeneration of collagen fibers 2) a fibroelas-tic spur along the coaptation surface 3) a decrease in the number of cuspal fibroblasts and in the amount of proteoglycans 4) accumulation of extracellular lipid (Figure 22.8) and 5) calcific deposits (Figure 22.9).27-29 Because of the prevalence of these changes, current donor criteria for allograft heart valves include an age restriction and a negative medical history of previous cardiac surgery, uncontrolled hypertension, functional cardiac murmurs, rheumatic fever and malignant, autoimmune or vascular

Viral Vectors for Gene Therapy Approach

For hypertension, where a long-term (or permanent) control of pathophysiology is the goal, integration of the transgene into the host cell's genome is necessary. Whereas naked DNA and liposomes are incapable of this task, viruses require such actions for their life cycle. Various viral vectors have been modified and used to deliver and incorporate transgenes of interest into cells. There are four major classes of viral vectors currently being used for both in vivo and in vitro applications in hypertension (Table 3). However, the ideal viral vector has yet to be found. An ideal vector should be safe (have a low toxicity when delivered), should not elicit an immune response, should integrate in a predictable, safe region of the genome, must be efficiently taken up by the target tissue, and must infect the target tissue with a high enough efficiency to have a physiological effect. For practical purposes, the vector also has to be packaged with high efficiency into the viral envelope, be...

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