Impaired Gene Expression of β_1-Adrenergic Receptor, but Not Stimulatory G-Protein Gsα, in Rat Ventricular Myocardium Treated with Isoproterenol(Pharmacology)

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We investigated the gene expression of β_1-adrenergic receptor (β_1AR) and stimulatory G-protein Gso, important signal transduction elements for regulating heart rate and contractility, in ventricle after chronic treatment with isoproterenol (ISO) in rat. Rats were treated with ISO (4 mg/kg, intraperitoneal) twice a day for 4 d. Ventricle weight of the heart and ventricle weight/body weight ratio were increased by 23% and 25% compared with control, respectively. Positive inotropic responses to ISO in left atrial muscle preparations isolated from ISO-treated rats were markedly decreased. Northern blot hybridization showed that the mRNA transcript of β_1AR was significantly decreased in ventricle of ISO-treated rats, whereas Gsα mRNA level was unchanged. Present results demonstrate that the gene expression of myocardial β_1AR, but not Gsα, was decreased in rat myocardium of ISO-induced cardiac hypertrophy, and suggesting that decrease in the gene expression of β_1AR may be one of the mechanisms responsible for the diminished cardiac function.
公益社団法人日本薬学会の論文
2004-07-01