Urotensin Expression in Hypertension and Heart Failure

A high density of urotensin receptors is found in the smooth muscle layer of coronary arteries and LV myocytes (69). Urotensin is approx 50 times more potent than ET-1 in 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.

Urotensin receptor gene expression increases in the heart 1 wk after experimental myocardial infarct in the rat compared with sham-operated controls (72). Positive staining for urotensin receptors is found in myocytes, ECs, and fibroblasts in the postinfarcted heart, and positive staining for urotensin is found in the infarcted region. This suggests a role for urotensin signaling in the remodeling process post-MI. Positive staining for urotensin protein is also observed in the myocardium of patients with end-stage heart failure (73). Staining is stronger in subendocardial myocytes compared with the subepicardium or midmyo-cardium. Furthermore, in patients with heart failure secondary to ischemic heart disease, urotensin immunoreactivity was significantly greater in the left ventricle compared with the right ventricle or atrial tissue. Urotensin protein expression positively correlates with LV end-diastolic dimension and inversely correlates with ejection fraction (both p < 0.001). Binding studies with labeled urotensin reveal a greater density of urotensin receptors in cardiac myocytes, ECs, and SMCs of hearts with end-stage failure compared with controls. These results were confirmed at the mRNA level for both urotensin and urotensin receptors, indicating that urotensin expression is upregulated in the hearts of patients with end-stage failure.

Plasma urotensin is increased in patients with NYHA class IV heart failure and correlates with plasma levels of ET-1 and adrenomedullin but not with angiotensin II, aldosterone, or norepinephrine (74). In patients with coronary artery disease (CAD), plasma urotensin correlates with NYHA class and LVEDP (75) (Fig. 7). Plasma aortic root urotensin levels are markedly elevated in patients with heart failure compared with patients with CAD and nonfailing hearts and inversely correlate with LVEF. Plasma levels in the aortic root are three- to fourfold higher than from the femoral artery, femoral vein, or pulmonary artery, suggesting cardiopulmonary production of urotensin in heart failure (76). In patients with CAD, Heringlake et al. (77) observed elevated urotensin levels in patients with elevated filling pressures and with three-vessel disease compared with both healthy subjects and patients with less severe disease and lower filling pressures. Urotensin levels were also significantly correlated to NT-proANP and NT-proBNP in this patient population.

Plasma urotensin levels are elevated in patients with heart failure but are unchanged with increasing NYHA class (78). Both plasma urotensin and BNP are independent predictors of NYHA class I heart failure (78).

Blood Pressure Health

Blood Pressure Health

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...

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