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

Woodman, Owen L
Pannangpetch, Patchareewan

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia

Correspondence: Dr OL Woodman, Department of Pharmacology, University of Melbourne, Parkville, Vic. 3052, Australia.

Received 22 March 1995; revision 24 May 1995; accepted 20 June 1995.

Clinical & Experimental Pharmacology & Physiology 23(1):p 50-56, January 1996.

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 α¹-adrenoceptor agonist phenylephrine (0.5-2 µg/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.