Metoprolol suppresses the development of ethanol-induced cardiac hypertrophy in the rat.
Subacute, severe intoxication with ethanol stimulates the peripheral sympathetic nervous system in the rat and enhances the excretion of adrenaline and noradrenaline. In association with this effect there is a rapid development of cardiac hypertrophy, with proportional heart weight increasing by 12% within 48 h. At this time adrenal medullary adrenaline content was depressed by more than 35%, whereas nonadrenaline content of the adrenal and heart were not affected. Metoprolol (20 mg/kg, t.i.d.) was without effect when used alone and had little if any impact on the ethanol-induced changes. Metoprolol (100 mg/kg, t.i.d.) reduced adrenal catecholamine content, but not cardiac noradrenaline content, and diminished cardiac weight in control animals. The combination of ethanol with the high dose of methoprolol enhanced the loss of medullary catecholamine and reduced cardiac noradrenaline content, whereas cardiac weight was the same as in control animals. A correlation between sympathetic activation and increasing cardiac mass and its antagonism by metoprolol implies a beta-adrenoceptor mediated link in the cardiac hypertrophy induced by ethanol.
Adams
M A
MA
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Hirst
M
M
D000311:Adrenal Glands / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000503:physiopathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control*; D002395:Catecholamines / Q000652:urine; D004837:Epinephrine / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D000431:Ethanol; D008790:Metoprolol; D009638:Norepinephrine; D004837:Epinephrine