Role of urotensin II, a novel vasoconstrictor factor, in cardiovascular disease

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Urotensin II (UII) is a newly discovered peptide that may play an important role in human health and disease. It has been found to be a potent constrictor (narrower) of blood vessels and therefore may be involved in diseases such as hypertension (high blood pressure) and heart failure (weak heart muscle disease). Furthermore, many other factors that constrict blood vessels have also been found to have effects on key organs, such as the heart. Our preliminary data suggests that this is also true of urotensin II. The proposal studies seek to determine the role of urotensin II in the : (i) periphery, by assessing contraction of forearm vessels to low doses of UII in normal volunteer subjects and patients with hypertension and heart failure; (ii) heart, by measuring expression of UII and its receptor in normal and failing human heart tissue; the UII response to experimental heart attack in the rat and in cell culture of important heart cells; (iii) general circulation, by measuring plasma levels in health and disease. The significance of this project is that if it is found that UII plays an important role in these diseases, then agents that block this system may represent a major therapeutic advance in the management of these diseases.