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.