INFLUENCE OF CALCIUM-CHANNEL BLOCKER TREATMENT ON THE MECHANICAL-PROPERTIES OF DIABETIC RAT MYOCARDIUM

The objective of this investigation was to determine whether calcium c hannel blocker (CCB) treatment effectively restores normal baseline me chanical function in diabetic myocardium and to evaluate its effect on the interval-strength relationship. Wistar rats were made diabetic wi th streptozotocin (55 mg/kg, IV). Left-ventricular papillary muscles f rom normal and diabetic (10 weeks) rats were superfused with Tyrode's solution at 30 degrees C. A subgroup of diabetic and normal animals re ceived daily injections of verapamil or nifedipine (10 mg/kg, IP; 8 we eks) to compare the effectiveness of a phenylalkylamine to a dihydropy ridine in reversing diabetes-induced contractile dysfunction in vitro. Muscles were electrically stimulated at 0.5 Hz with suprathreshold st imuli, and the following parameters were measured: peak tension develo ped, time-to-peak tension, time-to-90% relaxation, and the maximum vel ocities of tension development and decay. Experimental diabetes was ch aracterized by: severe hyperglycemia, hepatomegaly, reduced body weigh t gain, cardiomegaly, and increased plasma phospholipid levels. In add ition, baseline values of peak tension developed, time-to-peak tension , and time-to-90% relaxation were significantly greater in muscles fro m diabetic animals. Chronic nifedipine treatment reduced hyperglycemia and plasma phospholipid levels, normalized body weight gain, and redu ced both heart and liver sizes in diabetic animals. Nifedipine treatme nt completely reversed diabetes-induced prolongation in both time-to-p eak tension and time-to-90% relaxation. In diabetic myocardium, a slig htly positive component was present in the interval-strength relations hip between 0.01 and 1 Hz, resulting in a rightward shift in the entir e curve across a wide range of stimulation frequencies (0.01-5 Hz). Th is positive component was absent in muscles from diabetic animals trea ted with both CCBs, and verapamil produced a leftward shift in the fre quency-response curve. The results of this study suggest that chronic nifedipine treatment may be more effective than verapamil in restoring normal baseline myocardial mechanical function, reducing hyperglycemi a and hyperlipidemia, as well as attenuating both cardiac and liver en largement in experimental diabetes. In contrast, verapamil treatment t ended to normalize more effectively the inotropic response to changes in stimulation frequency in diabetic myocardium.