PLASMA LEVELS OF UROTENSIN II AND ITS URINARY EXCRETION IN PATIENTS WITH DIABETES MELLITUS : RELATION WITH DIABETIC NEPHROPATHY

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Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. The potency of the vasoconstriction of UII is an order of magnitude greater than that of endothelin-1 and angiotensin II. In order to clarify the pathophysiological role of UII in the progression of organ damages, we examined plasma UII levels, urinary excretion of UII, and mRNA expression of UII in various organs.Results:1.We newly developed a radioimmunoassay specific to human UII, and examined plasma UII levels in patients with various diseases. Plasma UII levels were elevated in patients with chronic renal failure (Lancet 2001). Patients with type-2 diabetes mellitus also had elevated plasma UII levels (Clin Sci 2003). Urinary examination showed that diabetes itself was a factor to elevate plasma UII levels and the renal failure, not proteinuria, was another isolated factor to increase plasma UII levels (Peptides 2004 (in press)). Patients with heart failure and those with hypertension secondary to endocrine diseases such as pheochromocytoma, primary aldosteronism and Cushing syndrome also had increased plasma UII levels.2.UII mRNA was expressed not only in brain but also in the various peripheral organs of humans and rats.3.We examined UII mRNA expression in hearts and kidneys of rats with 5/6 renal mass ablation or acute myocardial infarction after coronary ligation.4.Expression of UII mRNA in cultured human endothelial cells was increased by hypoxia, suggesting that UII has an important roles the progression of renal ischemic injury.5.UII has a proliferative effect on cultured human tumor cell lines (Clin Sci 2002).