Influence of low perfusion pressure on effect of endothelin on coronary vascular bed.
The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche, Basel, Switzerland.
Sprecher
U
U
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008863:Microspheres; D010477:Perfusion; D011312:Pressure
D016232:Endothelins; D000804:Angiotensin II