Effects of endothelin on the coronary vascular bed in open-chest dogs.
The goal of the present study was to evaluate the effects of endothelin, a newly discovered very potent vasoconstrictor secreted by endothelial cells, on the coronary vascular bed. For this purpose, the effects of endothelin injected intracoronarily were tested in open-chest anesthetized dogs with the circumflex coronary artery cannulated and perfused at a constant pressure of 100 mm Hg. Circumflex blood flow, transmural distribution of coronary blood flow (radioactive microspheres), circumflex coronary artery diameter (piezoelectric crystals), and circumflex luminal surface area were measured. Endothelin decreased coronary blood flow by 30% and 61% with doses of 1 and 3 micrograms, respectively. A dose of 10 micrograms was lethal. The decrease of coronary blood flow was larger in the subepicardium than in the subendocardium, which explains that the endocardial-epicardial blood flow ratio increased from 1.27 +/- 0.05 to 1.98 +/- 0.23 (p less than 0.001) with a dose of 3 micrograms endothelin. Circumflex surface area decreased by 7% (p = NS) and 20% (p less than 0.01) with doses of 1 and 3 micrograms endothelin, respectively. The action of endothelin was not modified by the concomitant alpha-adrenergic blockade, serotonergic blockade, angiotensin converting enzyme inhibition, or cyclooxygenase inhibition. We conclude that endothelin is a potent coronary vasoconstrictor with a selective effect on the subepicardium. At least part of the increase of coronary vascular resistance is due to a constriction of the large coronary arteries. Further studies are required to determine the physiopathological role of endothelin, especially in coronary vasospasm.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
Clozel
M
M
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects; D004285:Dogs; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010455:Peptides