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

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional differences in the density and subtype specificity of endothelin receptors in rabbit urinary tract

“…It has been reported that an intravenous bolus injection of ET results in an early transient depressor response followed by a sustained pressor response in anesthetized animals (Inoue et al 1989;Minkes et al 1989), and that selective ETA receptor antagonists attenuate only the pressor effect of ET Miyata et al 1992). In rat isolated perfused mesentery, ET-1 was several times more potent than ET-3 in inducing vasoconstriction, whereas ET-3 was more potent than ET-1 in inducing a vasodilation response in these vessels (Minkes et al 1989;Warner et al 1989).…”

“…It has been reported that an intravenous bolus injection of ET results in an early transient depressor response followed by a sustained pressor response in anesthetized animals (Inoue et al 1989;Minkes et al 1989), and that selective ETA receptor antagonists attenuate only the pressor effect of ET Miyata et al 1992). In rat isolated perfused mesentery, ET-1 was several times more potent than ET-3 in inducing vasoconstriction, whereas ET-3 was more potent than ET-1 in inducing a vasodilation response in these vessels (Minkes et al 1989;Warner et al 1989). The ET-3 induced vasodilation is considered to be mediated through activation of ETB receptors with subsequent release of vasodilator substances such as endotheliumderived relaxing factor (EDRF), nitric oxide (NO), or prostacyclins from the endothelium (de Nucci et al 1988;Warner et al 1989).…”

Application of monoclonal antibodies for endothelin to hypertensive research.

“…Human big ET (human ET ) and a common carboxy terminal fragment of ET (ET [17][18][19][20][21]) were synthesized by the solid phase method. 6 …”

Effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine on the vasoactive effects of endothelin-3.

“…Yanagisawa et al (1) found that ET con stricted rat aortic strips in a dose-dependent manner, where the initial dose for constriction was 10-" M and the EC50 was 5 6 X 10' M. However, it has been reported that in travenous bolus injection of ET (0.1 to 3 nM/kg) causes a transient, dose-related de pressor response (2,3). Even in in vitro ex periments, vasodilating effects of ET, particu larly at low doses, have been demonstrated (4)(5)(6).…”