Diminished Responsiveness to Cardiac β_1-Adrenoceptor Agonists in Rats with Chronic Heart Failure Following Myocardial Infarction

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The present study was undertaken to determine whether cardiac response to β_1-adrenergic agonists is altered in rats with chronic heart failure (CHF), and whether this alteration is related to β-adrenergic receptor down-regulation in the viable tissue of the left ventricle of these rats. For this purpose, the cardiac response to denopamine, a selective β_1-adrenergic agonist, and the change in cardiac β-adrenoceptor density were examined in rats with CHF. A non-selective β-adrenergic agonist, isoprenaline, was also examined as a comparison. Cardiac output and stroke volume indices were reduced 12 weeks after left coronary artery ligation, suggesting that CHF had developed at this time. Denopamine (2,4 and 8μg/kg i.v.), and isoprenaline (0.01μg/kg i.v.) increased the cardiac output and stroke volume indices in sham-operated rats, whereas such increases were attenuated in the CHF rat. The cardiac β-adrenergic receptor density, measured by [^3H] CGP-12177 binding assay, was reduced in homogenates and microsomal membranes in the viable tissue of the left ventricle of the CHF rat (homogenates : 29% reduction, microsomal membrane : 23% reduction). These results suggest that the cardiac responsiveness to denopamine is diminished in the CHF rat and this alteration is accounted for, in part, by a decrease in cardiac β-adrenoceptor density.
社団法人日本薬学会の論文
1995-10-15