The coronary vasodilator effect of neurotensin in the guinea pig isolated heart.

Neurotensin (NT) infusions into isolated, electrically-driven hearts of guinea pigs, elicited concentration-dependent reductions of myocardial perfusion pressure accompanied by proportional increases of myocardial tension. The decrease of myocardial perfusion pressure caused by NT (attributed to the coronary vasodilator effect of NT) was highly dependent on basal (pre-NT infusions) levels of perfusion pressure, being larger at high perfusion pressure (e.g., 75 mmHg) values than at lower ones (e.g., 50 and 25 mmHg). The perfusion pressure-lowering effect on NT was potentiated and inhibited by neostigmine and atropine, respectively. It was slightly inhibited by methysergide. However, it was not affected by propranolol, indomethacin or a mixture of diphenhydramine and cimetidine. The decreases of myocardial perfusion pressure caused by NT were abolished by NT receptor desensitization, while those evoked by acetylcholine or vasoactive intestinal peptide (VIP) were minimally affected by the desensitization. These results indicate that NT exerts a vasodilator effect in guinea pig coronary vessels. This effect is likely to involve the participation of acetylcholine released from NT-stimulated cardiac cholinergic (vagal) neurons and/or nerve terminals and to be mediated by specific NT receptors. The possible contribution of intracardiac serotonin and/or its receptors to the coronary vasodilator effect of NT is discussed.