Influence of genetically predisposed diabetes on ethanol-induced depression of cardiac contraction in adult rat ventricular myocytes.
Diabetes mellitus and alcohol (ethanol) intake are two positively correlated major risk factors for cardiovascular abnormalities. However, the interaction of the two on cardiac function is largely unknown. The purpose of the present study was to examine the impact of genetically predisposed diabetes on acute ethanol exposure-induced cardiac contractile depression at the myocyte level. Ventricular myocytes from spontaneously biobreeding diabetes-prone (BBDP) rats and their diabetes-resistant littermates (BBDR) were stimulated to contract at 0.5 Hz. Contractile properties analysed include: peak shortening amplitude (PS), time-to-PS (TPS), time-to-90 % relengthening (TR(90)) and maximal velocities of shortening/relengthening (+/- dL/dt). BBDP rats displayed hyperglycaemia, reduced body weight gain and increased cardiac, hepatic and renal size. Myocytes isolated from BBDP rat hearts exhibited prolonged TPS and TR(90) associated with normal PS and +/- dL/dt, compared with myocytes from the BBDR group. Acute ethanol exposure (80-640 mg dl(-1)) caused a concentration-dependent inhibition of PS in both BBDR and BBDP myocytes. However, the degree of inhibition of PS was significantly reduced in BBDP myocytes compared to that of BBDR myocytes. The maximal inhibition was 52.9 % and 28.4 % in BBDR and BBDP groups, respectively. Ethanol significantly depressed +/- dL/dt in both BBDR and BBDP myocytes. In addition, ethanol did not affect TPS or TR(90) in either the BBDR or BBDP group. Collectively, these results suggest that the ethanol-induced depression in cardiac myocyte contraction may be 'shadowed' by genetically predisposed diabetes.
Ren
Jun
J
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203, USA. jren@medicine.nodak.edu
D008841:Actin Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D002118:Calcium / Q000502:physiology; D002469:Cell Separation; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000431:Ethanol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000473:pathology; D016276:Ventricular Function
D002492:Central Nervous System Depressants; D000431:Ethanol; D002118:Calcium