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 dysfunction has been attributed, in part, to calcium overload within individual myocytes. The present study compares the effectiveness of the calcium channel blocker nifedipine (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing myocardial dysfunction and diminishing the negative inotropic effect of ethanol on diabetic rat myocardium. Wistar rats were made diabetic with streptozotocin (55 mg/kg, i.v.) and isolated electrically stimulated papillary muscles were studied under isometric conditions in the absence and presence of clinically relevant concentrations of ethanol (80-240 mg/dl, i e., 17.4-52.1 mM). Subgroups of diabetic and normal animals received daily injections of verapamil or nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic animals exhibited hyperglycemia, hyperlipidemia, reduced growth, cardiomegaly, and hepatomegaly. Compared to verapamil chronic nifedipine treatment normalized or reversed the effects of diabetes on myocardial mechanical function. The negative inotropic effect of ethanol was attenuated only in muscles from verapamil-treated diabetic 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 experimental diabetes. However, chronic verapamil therapy is more effective in diminishing the negative inotropic effect of ethanol on diabetic myocardium. These findings may have clinical significance among diabetic patients who consume alcoholic beverages while receiving long-term calcium blocker therapy.
Brown
R A
RA
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA. rbrown@med.wayne.edu
Sundareson
A M
AM
Lee
M M
MM
Savage
A O
AO
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004336:Drug Antagonism; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D000431:Ethanol; D014700:Verapamil; D009543:Nifedipine