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 treatment attenuates the negative inotropic effect of ethanol (EtOH) in the diabetic rat heart. Wistar rats were made diabetic with streptozotocin (55 mg/kg, iv). Left-ventricular papillary muscles, from normal and diabetic (8 weeks) rats, were superfused with Tyrode's solution at 30 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 microM) in vitro. Peak tension developed (PTD), time to peak tension (TPT), time to 90% relaxation (RT90), and the maximum velocities of tension development (+VT) and decay (-VT) were determined in the absence and presence of clinically relevant concentrations of EtOH (80-240 mg/dL, 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 EtOH (120-240 mg/dL) decreased PTD, TPT, +VT, and -VT. The negative inotropic effect of EtOH (240 mg/dL) was attenuated only in diabetic myocardium chronically treated with verapamil, whereas acute verapamil treatment potentiated the negative inotropic effect of EtOH in both normal and diabetic myocardium. Thus, chronic verapamil therapy diminishes the negative inotropic effect of EtOH in diabetic myocardium and acute verapamil treatment exaggerates it.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201.
R A
RA
Brown
P
P
Bhasin
A O
AO
Savage
J C
JC
Dunbar
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
D000431:Ethanol; D013311:Streptozocin; D014700:Verapamil