Endothelin-1-induced constriction in the coronary resistance vessels and abdominal aorta of the guinea pig

Abstract

The purpose of this study was to examine contractile properties of endothelin-1, a newly discovered vasoactive peptide, in guinea pig coronary resistance vessels and abdominal aorta. Changes in perfusion pressure after injections of endothelin-1 were measured using a constant-flow modified Langendorff preparation. The ED 10 values of coronary perfusion pressure were about 100-fold less for endothelin-1 than for prostaglandin F 2α . After the endothelium was damaged by exposure to free radicals, maximal coronary constriction in response to endothelin-1 (10 −9 moles) was not altered, whereas dilator responses to low doses of endothelin-1 were converted to constrictor responses. Removal of the endothelium from aortic rings significantly increased responsiveness to endothelin-1 and the maximal response to the peptide. In calcium-free medium, endothelin-1 induced small increases both in perfusion pressure in coronary vessles and in tension in the aorta. Reintroduction of calcium in the coronary and aortic preparations produced a rapid increase in perfusion pressure and tension, respectively. Further, endothelin-1-induced coronary constriction was inhibited 59%±7% by nifedipine (10 −7 moles). We conclude that endothelin-1 is a more potent constrictor than prostaglandin F 2α in the coronary vasculature. Endothelin-1-induced constriction in the coronary vasculature of the guinea pig is not mediated through an endogenous constricting factor released from the endothelium or a constrictor prostaglandin. Further, endothelin-1-induced dilation in the coronary vasculature and attenuation of endothelin-1-induced contraction in the abdominal aorta of the guinea pig are mediated through the release of a factor from the endothelium. Endothelin-1-induced coronary constriction and abdominal aortic contraction require extracellular calcium, entering, in part, through nifedipine-sensitive channels.