EFFECT OF ENDOTHELIN ON NORMAL AND DISEASED HUMAN CORONARY-ARTERIES

We have examined the action of endothelin on healthy and diseased human epicardial coronary arteries to assess its possible role in coronary vascular disorders such as vasospasm and atherosclerosis. Endothelin (10(-10) mol l-1-10(-7) mol l-1) produced dose-dependent contractions in both normal and diseased vessels. The level of constriction was significantly greater in healthy vessels at 10(-8) mol l-1 endothelin. A greater response was recorded in smaller, more distal vessel segments, irrespective of the pathology of the tissue. Endothelium denudation of disease-free segments had no significant effect on the response to endothelin. In the presence of a threshold dose of endothelin (10(-9) mol l-1), there was no measurable increase in the tension generated by potassium chloride, the thromboxane-mimetic U46619, noradrenaline and histamine. However, the response to 5-HT showed a large increase in arteries from four patients (440-147%) but slight or no increase in arteries from another three patients. We conclude that the interaction with other vasoconstrictor substances is a possible mechanism whereby endothelin may be involved in coronary artery vasospasm. In addition, endothelin may also be involved in the regulation of vascular tone of the small vessels of the heart.