Changes in myocardial β1-adrenergic receptor and stimulatory G-protein gene expression after chronic treatment with doxorubicin in rat

Abstract

The gene expression of β1-adrenergic receptor (β1AR) and stimulatory G-protein Gsα in ventricle after chronic treatment with doxorubicin (DOX) in rat was investigated. The rats were treated with DOX in a dose of 2.5 mg/kg once a week for 5 weeks, the c umulative dose being 12.5 mg/kg. Two weeks after the last injection, the positive inotropic effect of isoproterenol was noticeably decreased in left atrial muscle preparations isolated from DOX-treated rats. Northern blot hybridization showed that the mRNA transcripts of β1AR and Gsα, important signal transduction elements for regulating heart rate and contractility, were significantly decreased in the ventricle of DOX-treated rats. Thus, chronic treatment with DOX decreases the gene expression levels of myocardial β1AR and Gsα.