Endothelin-1-induced constriction in the coronary resistance vessels and abdominal aorta of the guinea pig.
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 ED10 values of coronary perfusion pressure were about 100-fold less for endothelin-1 than for prostaglandin F2 alpha. 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 vessels 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 F2 alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Folta
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A
Department of Physiology, University of Michigan, Ann Arbor 48109.
Joshua
I G
IG
Webb
R C
RC
D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D016232:Endothelins / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D002118:Calcium