Renal Sodium & Fluid Retention
FIGURE 6-10 Formation of angiotensin II and its effects on renal, vascular, and cardiac function. Renin is released by the kidneys in response to sympathetic stimulation, hypotension, and decreased sodium delivery to distal tubules. Renin acts upon angiotensinogen to form angiotensin I (A!), which is converted to angiotensin II (All) by angiotensin-converting enzyme (ACE). AII has several important actions: it stimulates aldosterone release, which increases renal sodium reabsorption; directly stimulates renal sodium reabsorption; stimulates thirst; produces systemic vasoconstriction; and causes cardiac and vascular smooth muscle hypertrophy. The overall systemic effect of increased AII is increased blood volume, venous pressure, and arterial pressure.
Angiotensin II is continuously produced under basal conditions, and this production can change under different physiologic conditions. For example, when a person exercises, circulating levels of angiotensin II increase. An increase in renin release during exercise probably results from sympathetic stimulation of the kidneys. Changes in body posture likewise alter circulating AII levels, which are increased when a person stands. As with exercise, this results from sympathetic activation. Dehydration and loss of blood volume (hypovolemia) stimulate renin release and an-giotensin II formation in response to renal artery hypotension, decreased glomerular filtration rate, and sympathetic activation.
Several cardiovascular disease states are associated with changes in circulating angiotensin II. For example, secondary hypertension caused by renal artery stenosis is associated with increased renin release and circulating angiotensin II. Primary hyperal-dosteronism, caused by an adrenal tumor that secretes large amounts of aldosterone, increases arterial pressure through its effects on renal sodium retention. This increases blood volume, cardiac output, and arterial pressure. In this condition, renin release and circulating angiotensin II levels are usually depressed because of the hypertension. In heart failure, circulating angiotensin II increases in response to sympathetic activation and decreased renal perfusion. Therapeutic manipulation of the renin-angiotensin-aldosterone system has become important in treating hypertension and heart failure. ACE inhibitors and AT receptor blockers effectively decrease arterial pressure, ventricular afterload, blood volume, and hence ventricular preload, and they inhibit and reverse cardiac and vascular remodeling that occurs during chronic hypertension and heart failure.
Note that local, tissue-produced an-giotensin may play a significant role in cardiovascular pathophysiology. Many tissues and organs, including the heart and blood vessels, can produce renin and angiotensin II, which have actions directly within the tissue. This may explain why ACE inhibitors can reduce arterial pressure and cause cardiac and vascular remodeling (e.g., diminish hypertrophy) even in individuals who do not have elevated circulating levels of angiotensin II. In hypertension and heart failure, for example, tissue ACE activity is often elevated, and this may be the primary target for the pharmacologic actions of ACE inhibitors.
Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (p-adrenoceptor mediated). Therefore, elevated levels of ANP are found during conditions such as hypervolemia and congestive heart failure, both of which cause atrial distension.
ANP is involved in the long-term regulation of sodium and water balance, blood volume, and arterial pressure (Figure 6-11). Most of its actions are the opposite of angiotensin II, and therefore ANP is a counter-regulatory system for the renin-angiotensin-aldosterone system. ANP decreases aldosterone release by the adrenal cortex; increases glomerular filtration rate;
produces natriuresis and diuresis (potassium sparing); and decreases renin release, thereby decreasing angiotensin II. These actions reduce blood volume, which leads to a fall in central venous pressure, cardiac output, and arterial blood pressure. Chronic elevations of ANP appear to decrease arterial blood pressure primarily by decreasing systemic vascular resistance.
The mechanism of systemic vasodilation may involve ANP receptor-mediated elevations in vascular smooth muscle cGMP (ANP activates particulate guanylyl cyclase). ANP also attenuates sympathetic vascular tone. This latter mechanism may involve ANP acting upon sites within the central nervous system as well as through inhibition of norepi-nephrine release by sympathetic nerve terminals.
A new class of drugs that are neutral en-dopeptidase (NEP) inhibitors may be useful in treating heart failure. By inhibiting NEP, the enzyme responsible for the degradation of ANP, these drugs elevate plasma levels of ANP. NEP inhibition is effective in some models of heart failure when combined with
Atrial distension Sympathetic stimulation Angiotensin Endothelin i SVR
Was this article helpful?
Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...