title: Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats.
abstract: Recent evidence suggests that blockade of the renin-angiotensin 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 streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg x kg(-1) x day(-1) losartan for 8 weeks. Insulin and beta-adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the alpha-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (I(to)) were recorded in patch-clamped 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, beta-adrenergic-mediated enhancement of glucose uptake was completely recovered. APD and I(to) 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 cardiomyopathy.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Center of Molecular Medicine, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Raimondi
authors.forename: Petra
authors.initials: P
authors.lastname: De Paoli
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lonardo
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Grazia
authors.initials: G
authors.lastname: Banchelli
authors.forename: Renato
authors.initials: R
authors.lastname: Pirisino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
mesh_terms: D000200:Action Potentials; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
chemical_list: D057911:Angiotensin Receptor Antagonists; D005947:Glucose