ALTERED [H-3]OUABAIN BINDING TO CARDIAC-MUSCLE IN INSULIN-DEPENDENT AND NON-INSULIN-DEPENDENT DIABETIC RATS

The aim of this study was to determine the ouabain receptor density, N a+,K+-ATPase function and contractile properties of cardiac muscle in insulin-dependent and non-insulin-dependent rat diabetes mellitus (IDD M and NIDDM, respectively) and the reversibility of the diabetes-induc ed changes by insulin or thyroxin substitution. IDDM and NIDDM were in duced in Wistar rats by streptozotocin injection. Contractile paramete rs were measured in isolated left ventricular trabeculae. [H-3]Ouabain binding to myocardium was measured in right and left ventricular stri ps obtained from diabetic animals and their age-matched controls. Both the maximum [H-3]ouabain binding capacity (B-max) and the K-d for [H- 3]ouabain binding, as well as maximum Rb-86(+) uptake and rate of cont raction, were decreased in IDDM myocardium compared with controls. Ins ulin or thyroxin substitution reversed the reduction in B-max and cont raction rate, but not the decrease in K-d. In young, but not old, cont rol animals, both B-max and maximum Rb-86(+) uptake were higher in the right ventricular myocardium than in the left one. In contrast to cha nges observed in IDDM, both B-max and K-d for [H-3]ouabain binding wer e increased in the left but not in the right ventricle of NIDDM animal s. NIDDM caused no alterations in contractile properties. Prominent di fferences were observed in [H-3]ouabain binding characteristics and my ocardial contractility between young and old control animals. B-max of [H-3]ouabain binding and rate of contraction were inversely proportio nal in all preparations studied. It is concluded that IDDM and NIDDM i nduce different alterations in myocardial Na+,K+-ATPase, and these cha nges may influence the contractile properties of cardiac muscle.