β-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 β-adrenergic receptor and catecholamine-stimulaled adenylate cyclase activity was investigated in the slreptozotocin-diabetic rat. β-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 (I.V 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 I.V dP/dtmax to graded isoproterenol infusion. These studies suggest that alterations in β-adrenergic receptors and their coupling to adenylate cyclase may be important in the development of diabetic cardiomyopalhy.