title: Cardioprotective effect of propranolol on diabetes-induced altered intracellular Ca2+ signaling in rat.
abstract: We have previously shown that chronic treatment with propranolol had beneficial effects on heart function in rats during increasing-age in a gender-dependent manner. Herein, we hypothesize that propranolol would improve cardiac function in diabetic cardiomyopathy and investigated the benefits of chronic oral administration of propranolol on the parameters of Ca(2+) signaling in the heart of streptozotocin-diabetic rats. Male diabetic rats received propranolol (25 mg/kg, daily) for 12 weeks, 1 week after diabetes induction. Treatment of the diabetic rats with propranolol did not produce a hypoglycaemic effect whereas it attenuated the increased cell size. Basal and β-agonist response levels of left ventricular developed pressure were significantly higher in propranolol-treated diabetic rats relative to untreated diabetics while left ventricular end diastolic pressure of the treated diabetics was comparable to the controls. Propranolol treatment normalized also the prolongation of the action potential in papillary muscles from the diabetic rat hearts. This treatment attenuated the parameters of Ca(2+) transients, depressed Ca(2+) loading of the sarcoplasmic reticulum, and of the basal intracellular Ca(2+) level of diabetic cardiomyocytes. Furthermore, Western blot data indicated that the diabetes-induced alterations in the cardiac ryanodine receptor Ca(2+) release channel's hyperphosphorylation decreased the FKBP12.6 protein level. Also, the high phosphorylated levels of PKA and CaMKII were prevented with propranolol treatment. Chronic treatment with propranolol seems to prevent diabetes-related changes in heart function by controlling intracellular Ca(2+) signaling and preventing the development of left ventricular remodeling in diabetic cardiomyopathy.
authors: Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey.
authors: Erkan
authors: E
authors: Tuncay
authors: Esma N
authors: EN
authors: Zeydanli
authors: Belma
authors: B
authors: Turan
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000009:adverse effects / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D013311:Streptozocin; D011433:Propranolol