DIFFERENTIAL-EFFECTS OF CHRONIC CALCIUM-CHANNEL BLOCKER TREATMENT ON THE INOTROPIC RESPONSE OF DIABETIC RAT MYOCARDIUM TO ACUTE ETHANOL EXPOSURE

Cardiomyopathy is a consistent feature of diabetic myocardium as well as in prolonged alcohol consumption. Diabetes-induced myocardial dysfu nction has been attributed, in part, to calcium overload within indivi dual myocytes. The present study compares the effectiveness of the cal cium channel blocker nifedipine (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing myocardial dysfunction and dimini shing the negative inotropic effect of ethanol on diabetic rat myocard ium. Wistar rats were made diabetic with streptozotocin (55 mg/kg, IV) and isolated electrically stimulated papillary muscles were studied u nder isometric conditions in the absence and presence of clinically re levant concentrations of ethanol (80-240 mg/dl, ie., 17.4-52.1 mM). Su bgroups of diabetic and normal animals received daily injections of ve rapamil or nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic animals exhibited hyperglycemia, hyperlipidemia. r educed growth, cardiomegaly, and hepatomegaly. Compared to verapamil c hronic nifedipine treatment normalized or reversed the effects of diab etes on myocardial mechanical function. The negative inotropic effect of ethanol was attenuated only in muscles from verapamil-treated diabe tic animals. Thus, chronic nifedipine treatment may be more effective than verapamil in reducing hyperglycemia, attenuating both cardiac and liver enlargement, and restoring myocardial mechanical function, in e xperimental diabetes. However, chronic verapamil therapy is more effec tive in diminishing the negative inotropic effect of ethanol on diabet ic myocardium. These findings may have clinical significance among dia betic patients who consume alcoholic beverages while receiving long-te rm calcium blocker therapy.