Restoration of Cardiomyocyte Functional Properties byAngiotensin II Receptor Blockade in Diabetic Rats

Recent evidence suggests that blockade of the reninangiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocininduced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZinduced diabetic rats given vehicle or 20 mg kg1 day1 losartan for 8 weeks. Insulin and -adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the -adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (Ito) were recorded in patchclamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, -adrenergicmediated enhancement of glucose uptake was completely recovered. APD and Ito were similar to those measured in losartan-treated control rats. A significant (P < 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomy