Vasoconstrictor effect of endothelin on the canine coronary artery: is a novel endogenous peptide involved in regulating myocardial blood flow and coronary spasm?
We examined the effect of endothelin on the canine coronary artery (N = 20). The left circumflex coronary artery was cannulated and perfused with arterial blood at constant pressure. Coronary blood flow was monitored by an electromagnetic flowmeter. Intracoronary endothelin provoked a vasoconstriction that was dose-dependent. At a dose of 500 pmol, coronary blood flow was reduced remarkably (91.0 +/- 5.4%, n = 4), and endothelin subsequently produced a fall in systemic blood pressure and ST elevation in the electrocardiogram. At a dose of 100 pmol (n = 9), coronary flow decreased from 16.4 +/- 1.5 ml/min to 12.5 +/- 1.5 ml/min (p less than 0.001) and coronary vascular resistance increased from 6.3 +/- 0.8 mm Hg/ml/min to 9.9 +/- 1.9 mm Hg/ml/min (p less than 0.005). A cumulative dose-response curve to endothelin was obtained and the curves were shifted to the right after both verapamil and nifedipine administration. Therefore endothelin has a potent vasoconstrictor action that is attenuated by the calcium-channel blocker.
Igarashi
Y
Y
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Aizawa
Y
Y
Tamura
M
M
Ebe
K
K
Yamaguchi
T
T
Shibata
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003329:Coronary Vasospasm / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D016232:Endothelins; D004730:Endothelium, Vascular; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D014700:Verapamil; D009543:Nifedipine