The role of hypertension and left ventricular hypertrophy in diabetic cardiopathy is not yet defined. The issue is further complicated by the association of hypothyroidism and diabetes both clinically and experimentally. Diabetes, hypertrophy and hypothyroidism share a number of cardiac mechanical and biochemical effects in common. Specifically, each reduces left ventricular contractility and relaxation rate, decreases actomyosin and sarcoplasmic reticular (SR) Ca2+-ATPase activities, and shifts the predominant myosin isozyme subtype from V1 to V3. Preliminary studies showed that chronic (8 weeks) streptozotocin (STZ)-induced diabetes: 1) decreased left ventricular pulse pressure (LVPP) and contractility (LV+dP/dt) of spontaneously hypertensive (SH) rat hearts to a greater extent than it reduced LVPP and LV+dP/dt of normotensive Wistar Kyoto (WK) or Sprague-Dawley (SD) hearts, especially at high resistances to ejection; 2) decreased stroke work at high left atrial filling pressure of SH and WK hearts; 3) reduced relaxation rates (LV-dP/dt) of SH and normotensive rat hearts; 4) reduced SH rat arterial pressure and reversed SH rat heart hypertrophy; and 5) reduced prolyl hydroxylase activity of SH aortae to a greater extent than it reduced enzyme activity of normotensive rat aortae. Thus, SH rats may be predisposed to adverse cardiac effects of diabetes in spite of the progressive reduction in arterial pressure during diabetes. In addition, left ventricles of young (5 week old) nondiabetic SH rats have significantly higher ornithine decarboxylase (ODC) activity than do those of age-matched SD rats. The primary purpose of the proposed study is to characterize the effects of STZ-induced diabetes on cardiac performance, SR calcium transport, actomyosin Ca2+-ATPase activity, myosin isozyme distribution, and ventricular ultrastructure of SH rats. The secondary purpose is to explore possible mechanisms for the hypootensive and hypertrophy-reversing effects of diabetes, by further describing the changes in cardiac and vascular ornithine decarboxylase activity, and vascular collagen metabolism. The proposed study is designed to characterize the influences of animal age and duration of diabetes, as well as to distinguish between the effects of chronic diabetes from those of hypertrophy and hypothyroidism. The results will apply directly to the problems of diabetic cardiopathy, vascular complications of diabetes, and the pathogenesis of cardiac hypertrophy and chronic hypertension.
