Effect of alloxan- and streptozotocin-induced diabetes on isolated rat heart responsiveness to carbachol.

Autonomic neuropathy of the heart associated with a primary vagal dysfunction has been frequently found in chronic diabetic patients. Little is known about the responses of hearts obtained from experimentally induced diabetic animals to cholinergic agonists. We have studied the effects of carbachol on isolated perfused working hearts from alloxan- and streptozotocin-diabetic rats as well as hearts from age-matched controls at various time points after the induction of diabetes. Carbachol produced a dose-dependent (10(-8)-10(-5) or 3 x 10(-5) M) reduction in the basal rate of left ventricular pressure development (+dP/dt) in control and diabetic rat hearts at all of the time points studied. There was no change in the sensitivity of diabetic rat hearts to carbachol until about 30 days after induction of diabetes. Diabetic rat hearts exhibited a reduced sensitivity to carbachol at 100 days after induction compared to age-matched control hearts. Hearts isolated from diabetic rats at 180,240 and 360 days were more sensitive to carbachol compared with control hearts. A general decrease in sensitivity of the heart to carbachol was observed in both control and diabetic rats at 360 days. The results demonstrate that the sensitivity of diabetic myocardium changes as the disease state progresses. The alterations could be due to the development of an autonomic neuropathy in the heart.