CHRONIC VERAPAMIL TREATMENT ATTENUATES THE NEGATIVE INOTROPIC EFFECT OF ETHANOL IN DIABETIC RAT MYOCARDIUM

It is well established that cardiomyopathy is a consistent feature of diabetic myocardium and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. The objective of this investigation was to determine whether acute or chronic verapamil tre atment attenuates the negative inotropic effect of ethanol (EtOH) in t he diabetic rat heart. Wistar rats were made diabetic with streptozoto cin (55 mg/kg, iv). Left-ventricular papillary muscles, from normal an d diabetic (8 weeks) rats, were superfused with Tyrode's solution at 3 0 degrees C while driven at 0.5 Hz. A subgroup of diabetic and normal animals received daily injections of verapamil (8 mg/kg, ip; 8 weeks), whereas muscles from untreated animals were exposed to verapamil (2 m u M) in vitro. Peak tension developed (PTD), time to peak tension (TPT ), time to 90% relaxation (RT(90)), and the maximum velocities of tens ion development (+VT) and decay (-VT) were determined in the absence a nd presence of clinically relevant concentrations of EtOH (80-240 mg/d L, i.e., 17.4-52.1 mM). Ethanol at 80 mg/dL reduced PTD, +VT, and -VT only in preparations from diabetic animals. Higher concentrations of E tOH (120-240 mg/dL) decreased PTD, TPT, +VT, and -VT. The negative ino tropic effect of EtOH (240 mg/dL) was attenuated only in diabetic myoc ardium chronically treated with verapamil, whereas acute verapamil tre atment potentiated the negative inotropic effect of EtOH in both norma l and diabetic myocardium. Thus, chronic verapamil therapy diminishes the negative inotropic effect of EtOH in diabetic myocardium and acute verapamil treatment exaggerates it. Altered expression of membrane-bo und calcium channels may be involved in the negative inotropic respons e to EtOH in long-term diabetes.