INVOLVEMENT OF NITRIC-OXIDE IN CORONARY VASCULAR-RESPONSES TO 5-HYDROXYTRYPTAMINE IN THE ANESTHETIZED GREYHOUND

1. The effect of the intracoronary (i.c.) injection of 5-hydroxytrypta mine (5-HT; 0.1-1.0 mu g/kg) was examined before and after inhibition of nitric oxide (NO) synthesis with N-nitro-L-arginine (NOLA; 5 mg/kg i.c.) in nine anaesthetized greyhounds. Before administration of NOLA, 5-HT increased coronary blood flow (CBF) but decreased large coronary artery diameter indicating simultaneous dilatation of resistance vess els and constriction of large arteries. 2. The administration of NOLA significantly decreased large coronary artery diameter and increased s ystemic arterial pressure. There was no significant effect on coronary vascular resistance or heart rate. In the presence of NOLA, the 5-HT- induced constriction of the large coronary artery was enhanced and the dilatation of the resistance vessels was reduced. In addition there w as a secondary reduction in CBF, a response that was not observed befo re NOLA treatment.3. The response to NOLA suggests that a basal releas e of NO is important in the regulation of coronary and systemic vascul ar tone. Nitric oxide is an important mediator of coronary vasodilator responses to 5-HT, and in addition the release of NO modulates 5HT-in duced constriction of large coronary arteries.