Analysis of regional responses to endothelin in hindquarters vascular bed of cats

Regional responses to endothelin, a peptide derived from endothelial cells in culture, were investigated in the hindquarters vascular bed of cats, when flow varied naturally and when flow was maintained constant with a pump. Intravenous injections of endothelin at doses of 0.03 and 0.1 nmol/kg caused dose-dependent decreases in systemic arterial pressure and increases in distal aortic blood flow. Injection of endothelin at a dose of 0.3 nmol/kg iv caused a biphasic response characterized by an initial decrease in arterial pressure and an increase in blood flow, which was followed by a secondary rise in pressure and a fall in blood flow. When blood flow to hindquarters was maintained constant with a pump, intra-arterial injection of 0.03 nmol endothelin caused a decrease in perfusion pressure, whereas 0.1-1 nmol doses elicited biphasic responses characterized by an initial decrease followed by a secondary increase in perfusion pressure. When compared with other vasoactive peptides, the pressor activity of endothelin was less than angiotensin II by an order of magnitude but was threefold greater than that of neuropeptide Y in the hindquarters vascular bed. The pressor component of the response to endothelin and the response to the calcium agonist BAY K 8644 were decreased in a reversible manner by nisoldipine, a dihydropyridine calcium entry blocking agent. The results of these studies indicate that porcine-human endothelin has both vasodilator and vasoconstrictor activity in the hindquarters vascular bed of cats. The predominant response at a low concentration is vasodilation, whereas at higher concentrations a vasoconstrictor response that was dependent in part on the influx of extracellular calcium could be demonstrated. The present data suggest that endothelin could act as both an endothelium-derived vasodilating and vasoconstricting hormone in resistance vessels of the cat hindquarters.