Alterations in beta-adrenergic receptor density and cyclic-AMP level in the myocardium of rats chronically treated with alcohol.
An impaired function of the myocardial beta-adrenergic receptor system has been reported in patients with end-stage heart failure and this impairment has been postulated to be a factor in further deterioration of cardiac contractile function. As ventricular dysfunction is often associated with prolonged alcohol abuse, we investigated whether or not chronic administration of ethanol could induce alterations in the beta-adrenergic receptor adenylate-cyclase system in rats. Male Wistar rats of 8 weeks of age received 33% ethanol in drinking water for 3 months. As compared with control rats drinking water, the ethanol-treated rats showed weight loss and an increase in the heart/body weight ratio. Chronic ethanol increased myocardial contents of norepinephrine and epinephrine, possibly resulting from sympathoadrenal activation. The beta-adrenergic receptor density (Bmax) of the myocardial membrane was significantly decreased in the ethanol-treated rats (27.7 +/- 9.9 vs 39.0 +/- 6.0 fmol/mg protein, p < 0.01), while the affinity (Kd) did not differ between the two groups. The myocardial content of cyclic-AMP was also reduced in the ethanol rats (865 +/- 59 vs 1055 +/- 83 pmol/g w.w., p < 0.01). These observations indicate that chronic ethanol administration depresses the function of the beta-adrenergic receptor adenylate-cyclase system. The decreased beta-adrenergic receptor density was partly attributed to down-regulation due to increased sympathetic stimulation. This impaired function may contribute to the cardiac contractile dysfunction observed in chronic alcoholics.
Koga
Y
Y
Department of Medicine, Kurume University School of Medicine, Japan.
Kajiyama
K
K
Sufu
H
H
Otsuki
T
T
Tsuji
Y
Y
Iwami
G
G
Toshima
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D000242:Cyclic AMP