| Urotensin II (UII) is a vasoactive'somatostatin-like'cyclic peptide which was originally isolated from fish spinal cords, and has recently been cloned from man. The orphan receptor GPR14, a G-protein-coupled receptor first cloned from rat, has been defined as the specific receptor for UII. Positive immunoreactive staining for human UII and GPR14 mRNA was detected in both atrial and ventricular tissues. These studies indicate that UII might act as one of endogenous modulators of cardiac function. The cardiovascular action of UII has been examined in a number of in vitro and in vivo systems, sometimes with contrasting responses dependenting on the species and vessel studied. In mammals, UII was first reported to have a vasoconstrictor action in isolated rat thoracic aorta denuded of endothelium, an action that was later shown to be more potent than that of endothelin. UII was also shown to cause vasoconstriction in endothelium-denuded vessels from various species. In contrast, UII caused vasodilation in human small pulmonary arteries and abdominal adipose tissue arteries. In addition, the cardiovascular responses to UII in vivo are equally variable. Systemic administration of human UII to monkeys elicited a fall in cardiac output, severe myocardial contractility depression, and fatal circulatory failure. In anesthetized rats UII administered IV decreased arterial pressure. While in conscious rat IV UII reduced arterial pressure, the hypotension was associated with mesenteric and hindquarter vasodilatation. Although UII acts as a strong vasoactive peptide, it has been recently reported that central UII may play cardiovascular roles in the CNS, such as paraventricular nucleus of hypothamus (PVN), arcuate nucleus, A1 and A2 area. Intracerebroventricular (ICV) administration of UII significantly increased mean arterial pressure (MAP) and heart rate (HR) both in conscious rats and in anesthetized rats. Similarly, MAP and HR were increased after...
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