AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 598-H602, Copyright © 1989 by American Physiological Society
Analysis of regional responses to endothelin in hindquarters vascular bed of cats
R. K. Minkes, L. A. MacMillan, J. A. Bellan, M. D. Kerstein, D. B. McNamara and P. J. Kadowitz
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
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)
