beta-Adrenergic receptors, adenylate cyclase activity, and cardiac dysfunction in the diabetic rat

Cardiomyopathy is a complication of human diabetes mellitus. The relationship of cardiac function to the beta-adrenergic receptor and catecholamine-stimulated adenylate cyclase activity was investigated in the streptozotocin-diabetic rat. beta-Adrenergic receptor number in cardiac membranes from diabetic rats was reduced. After 2 weeks of diabetes, the response of adenylate cyclase to isoproterenol stimulation was not altered. Cardiac contractile function assessed by the maximum rate of rise of left ventricular pressure (LV dP/dtmax) in an open-chest anesthetized rat was also unchanged from control at 2 weeks. However, after 4 weeks of diabetes, the sensitivity of adenylate cyclase to isoproterenol stimulation was depressed and abnormalities in cardiac contractility were noted, including a depressed response of LV dP/dtmax to graded isoproterenol infusion. These studies suggest that alterations in beta-adrenergic receptors and their coupling to adenylate cyclase may be important in the development of diabetic cardiomyopathy.