N-NITRO-L-ARGININE AND INDOMETHACIN DO NOT AFFECT ENDOTHELIN-INDUCED CONSTRICTION OF LARGE AND SMALL CORONARY-ARTERIES IN THE ANESTHETIZED GREYHOUND

1. The aim of this study was to investigate whether endothelin-1 (ET-1 )-induced constriction of large and small coronary arteries in the ana esthetized greyhound is modulated by the endogenous release of nitric oxide or prostanoids. 2. ET-1 (1-100 ng/kg) and the alpha(1)-adrenocep tor agonist phenylephrine (0.5-2 mu g/kg), when injected directly into the circumflex coronary artery, caused dose-dependent decreases in ep icardial coronary artery diameter and coronary vascular conductance wi thout affecting systemic arterial pressure or the rate and force of ca rdiac contraction. 3. Inhibition of NO synthesis with N-nitro-L-argini ne (NOLA, 5 mg/kg, i.c.) decreased coronary artery diameter, coronary conductance and heart rate and increased arterial pressure. The corona ry vasoconstrictor response to ET-1 was unaffected by NOLA. By contras t, NOLA significantly increased the phenylephrine-induced constriction of the epicardial coronary artery but not the resistance vessels. 4. Indomethacin (5 mg/kg, i.v.), an inhibitor of cyclooxygenase, signific antly decreased epicardial coronary artery diameter but did not affect coronary conductance. Indomethacin had no effect on the coronary vasc ular responses to ET-1 or phenylephrine. Combined treatment with NOLA plus indomethacin also failed to affect the coronary vasoconstrictor e ffects of ET-1. 5. Basal release of NO and vasodilator prostanoids mod ulated resting coronary vascular tone but did not influence the vasoco nstrictor responses to endothelin in either large or small coronary ar teries.