Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure

Abstract

Human urotensin-II (hU-II) is the most potent endogenous cardiostimulant identified to date. We therefore determined whether hU-II has a possible pathological role by investigating its levels in patients with congestive heart failure (CHF). Blood samples were obtained from the aortic root, femoral artery, femoral vein, and pulmonary artery from CHF patients undergoing cardiac catheterization and the aortic root from patients undergoing investigative angiography for chest pain who were not in heart failure. Immunoreactive hU-II (hU-II-ir) levels were determined with radioimmunoassay. hU-II-ir was elevated in the aortic root of CHF patients (230.9 +/- 68.7 pg/ml, n = 21; P < 0.001) vs. patients with nonfailing hearts (22.7 +/- 6.1 pg/ml, n = 18). This increase was attributed to cardiopulmonary production of hU-II-ir because levels were lower in the pulmonary artery (38.2 +/- 6.1 pg/ml, n = 21; P < 0.001) than in the aortic root. hU-II-ir was elevated in the aortic root of CHF patients with nonischemic cardiomyopathy (142.1 +/- 51.5 pg/ml, n = 10; P < 0.05) vs. patients with nonfailing hearts without coronary artery disease (27.3 +/- 12.4 pg/ml, n = 7) and CHF patients with ischemic cardiomyopathy (311.6 +/- 120.4 pg/ml, n = 11; P < 0.001) vs. patients with nonfailing hearts and coronary artery disease (19.8 +/- 6.6 pg/ml, n = 11). hU-II-ir was significantly higher in the aortic root than in the pulmonary artery and femoral vein, with a nonsignificant trend for higher levels in the aortic root than in the femoral artery. The findings indicated that hU-II-ir is elevated in the aortic root of CHF patients and that hU-II-ir is cleared at least in part from the microcirculation.

Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

“…The observation that basal hemodynamics and general vasopressor responsiveness are unaltered in UT knockout mice supports the suggestion that the receptor is functionally silent under basal conditions, but this may change in cardiovascular diseases (13). In addition to elevated levels in patients with heart failure, systemic hypertension, diabetes mellitus, and renal failure (14,15), increased plasma UII levels have been reported in patients with cirrhosis (16,17).…”

“…To address the issue of UII in the pathogenesis of portal hypertension, our group determined UII levels in patients with cirrhosis without hepatorenal syndrome, systemic hypertension, diabetes and hemodynamic instability secondary to variceal bleeding. UII levels in patients with heart failure, systemic hypertension, diabetes mellitus and renal failure are elevated (14,15), therefore, patients with diabetes mellitus, chronic kidney disease, systemic hypertension, and aortic valvular disease were excluded. UII circulates in the human plasma and its concentration is measured by ELISA using specific antibodies.…”

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

“…Alternatively, in certain pathological conditions including diabetes (24)(25)(26)(27)50), the plasma concentrations of UII may attain much higher levels (140-420 pg/ml) that are in the same range as the IC 50 value (120 pmol/l i.e. 167 pg/ml) calculated for the insulinostatic activity of UII, suggesting that UII might constitute a diabetogenic factor.…”

“…Immunoreactive UII is readily measurable in human plasma, and the circulating levels of UII are elevated in patients with chronic renal failure (24) and heart failure (25,26). Plasma UII levels are also increased in diabetic patients with or without proteinuria, but are not correlated with fasting blood glucose or HbA1c levels (27).…”

Is plasma urotensin II concentration an indicator of myocardial damage in patients with acute coronary syndrome?

“…The response to UII administration in vivo and in vitro is differentiated in vascular beds [3]. Urotensin II is considered to be a more potent vasoconstrictor and cardiostimulant than endothelin-1, but in some conditions it becomes a vasodilator [4][5][6][7]. Furthermore, UII has an inotropic effect in humans and rats [8].…”