Vasoconstriction produced by intracoronary cholinomimetic drugs in isolated donor-perfused hearts of rhesus monkeys: comparison with pig, dog, and rabbit hearts.

The actions of cholinomimetic drugs on the coronary vasculature in rhesus monkeys were compared with those in miniature pigs, beagle dogs. and rabbits. The studies were performed on spontaneously beating hearts isolated in situ whose coronary vasculature was perfused at a fixed flow rate with heparinized arterial blood from donor animals via retrograde flow through the brachiocephalic artery. Single doses of drugs were injected into the coronary perfusion system via an aortic cannula. Bolus injections of acetylcholine, bethanechol, and methacholine decreased left ventricular systolic pressure and heart rate in all species in a dose-dependent fashion. In hearts of dogs and rabbits, these cholinomimetic drugs caused only vasodilation. In hearts of monkeys and pigs, however, bethanechol and methacholine produced prominent vasoconstriction as well as vasodilation. Acetylcholine in large doses elicited transient vasoconstriction followed by vasodilation in monkey hearts, but not in pig hearts. Coronary vasoconstriction in response to acetylcholine, bethanechol, and methacholine was not significantly affected by phentolamine, but was fully antagonized by atropine. The results indicate species differences in the response of the coronary circulation to cholinomimetic drugs. Rhesus monkeys resemble rats in this regard.