Cholinergic supersensitivity and decreased number of muscarinic receptors in atria from short-term diabetic rats.

Autonomic neuropathy is a major complication of chronic diabetes and is responsible for disturbances in the cardiovascular system and other organs. Early cardiac disturbances have been attributed to defective vagal control of the heart. The heart rates of rats with chemically-induced diabetes are depressed and an increase in blood pressure produces a greater reflex bradycardia in diabetic rats. Tomlinson and Yusof found that isolated, stimulated left atria from rats made diabetic with alloxan are supersensitive to the negative inotropic influence of acetylcholine. On the other hand, Rao, et al. found that perfused working-heart preparations from streptozotocin- and alloxan-diabetic rats have a reduced sensitivity to carbamylcholine. In the present study, we measured chronotropic responses to cholinergic agonists of isolated, spontaneously-beating atria, as well as muscarinic receptor populations, in cardiac tissue from short-term (8 to 9 weeks) diabetic and age-matched control rats.