Desensitization of myocardial but not coronary VIP receptor-mediated responses in dogs

Desensitization to the hemodynamic effects of vasoactive intestinal polypeptide (VIP) was examined in 12 anesthetized, open-chest dogs in which cardiac output, systemic arterial resistance, and heart rate were fixed. VIP was administered by intracoronary infusion, and the effects were compared with isoproterenol and forskolin. Measurements of left ventricular maximum rate of pressure development (dP/dt), coronary blood flow, and myocardial oxygen consumption were made before and after a 90-min infusion of either isoproterenol (6 dogs) or VIP (6 dogs). After isoproterenol infusion, there was a significant decrease in the effect of isoproterenol on left ventricular dP/dt and coronary blood flow. The effects of VIP and forskolin were not changed. After VIP infusion, there was a significant decrease in the effect of VIP on left ventricular dP/dt with no change in the effects of isoproterenol and forskolin. In this group, a significant increase in coronary blood flow with minimal change in myocardial oxygen could still be elicited by VIP injection after VIP infusion. The agonist infusion time to achieve a decrease in inotropic effect was less for VIP when compared with isoproterenol. Thus these data demonstrate acute homologous desensitization of myocardial VIP and beta-adrenergic receptors in canine myocardium with no development of heterologous desensitization, desensitization involving the catalytic subunit of adenylate cyclase, or desensitization of the VIP-mediated primary coronary vasodilator response.