Basis for myocardial mechanical defects associated with non-insulin-dependent diabetes.
Hearts isolated from 12-mo non-insulin-dependent diabetic rats exhibited reduced rates of contractility and relaxation. Associated with the abnormality in contractility was a redistribution in myosin isozyme content to the least active V3 form. Defects in myocardial relaxation also occurred concomitantly with impaired handling of calcium. Total tissue calcium content rose 35% in the diabetic hearts. At the same time, the activity of the pump responsible for maintaining normal cytoplasmic calcium levels was reduced. At a free calcium concentration of 2.0 microM, the rates of sarcoplasmic reticular calcium uptake and adenosinetriphosphatase activity of the diabetic hearts were decreased approximately 30%. Diastolic ventricular stiffness increased dramatically. The net result of these abnormalities in calcium metabolism is a significant impairment in mechanical performance of the diabetic heart.
Schaffer
S W
SW
Department of Pharmacology, University of South Alabama School of Medicine, Mobile 36688.
Mozaffari
M S
MS
Artman
M
M
Wilson
G L
GL
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006706:Homeostasis; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D009218:Myosins / Q000378:metabolism; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D009124:Muscle Proteins; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D002118:Calcium