N-nitro-L-arginine and indomethacin do not affect endothelin-induced constriction of large and small coronary arteries in the anaesthetized 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 anaesthetized greyhound is modulated by the endogenous release of nitric oxide or prostanoids. 2. ET-1 (1-100 ng/kg) and the alpha1-adrenoceptor agonist phenylephrine (0.5-2 mu g/kg), when injected directly into the circumflex coronary artery, caused dose-dependent decreases in epicardial coronary artery diameter and coronary vascular conductance without affecting systemic arterial pressure or the rate and force of cardiac contraction. 3. Inhibition of NO synthesis with N-nitro-L-arginine (NOLA, 5 mg/kg, i.c.) decreased coronary artery diameter, coronary conductance and heart rate and increased arterial pressure. The coronary vasoconstrictor response to ET-1 was unaffected by NOLA. By contrast, 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 cyclo-oxygenase, significantly decreased epicardial coronary artery diameter but did not affect coronary conductance. Indomethacin had no effect on the coronary vascular responses to ET-1 or phenylephrine. Combined treatment with NOLA plus indomethacin also failed to affect the coronary vasoconstrictor effects of ET-1. 5. Basal release of NO and vasodilator prostanoids modulated resting coronary vascular tone but did not influence the vasoconstrictor responses to endothelin in either large or small coronary arteries.
Woodman
O L
OL
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Pannangpetch
P
P
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology
D019332:Endothelin-1; D010656:Phenylephrine; D001120:Arginine; D007213:Indomethacin