β-Adrenergic Receptors, Adenylate Cyclase Activity, and Cardiac Dysfunction in the Diabetic Rat

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Abstract
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 wk 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 wk. However, after 4 wk 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. Alterations in .beta.-adrenergic receptors and their coupling to adenlyate cyclase may be important in the development of diabetic cardiomyopathy.