Effects of Insulin on Coronary Blood Flow in Anesthetized Pigs

Abstract

Insulin can influence the vasculature by a sympathetically mediated vasoconstriction and a vasodilatation; the latter effect predominates in the renal circulation of anesthetized pigs. We determined the effect of intravenous infusion of insulin on coronary blood flow in pentobarbitone-anesthetized pigs at constant heart rate, arterial pressure and blood levels of glucose and potassium. In 6 pigs, infusion of 0.004 IU kg^–1 min^–1 of insulin decreased coronary flow despite increasing left ventricular d P d t_max^–1; when the latter was abolished by propranolol, the coronary flow response was augmented. The mechanisms of this response were examined in 22 pigs given propranolol. Phentolamine changed coronary flow response to an increase (6 pigs) and this was abolished by intracoronary injection of N^ω-nitro- L-arginine methyl ester (L-NAME; 5 pigs). L-NAME augmented coronary flow response (6 pigs) and this was abolished by phentolamine (5 pigs). In 18 pigs given propranolol, three incremental doses of insulin caused graded coronary flow decreases whether L-NAME was given (6 pigs) or not (6 pigs) beforehand, and caused graded coronary flow increases after phentolamine (6 pigs). Thus insulin caused a coronary vasoconstriction mediated by sympathetic α-adrenergic effects and a vasodilatation related to the release of nitric oxide. The net effect was a coronary vasoconstriction.