Diminished responsiveness to cardiac beta 1-adrenoceptor agonists in rats with chronic heart failure following myocardial infarction

Biological & Pharmaceutical Bulletin
A Sanbe, S Takeo

Abstract

The present study was undertaken to determine whether cardiac response to beta 1-adrenergic agonists is altered in rats with chronic heart failure (CHF), and whether this alteration is related to beta-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 beta 1-adrenergic agonist, and the change in cardiac beta-adrenoceptor density were examined in rats with CHF. A non-selective beta-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 8 micrograms/kg i.v.), and isoprenaline (0.01 microgram/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 beta-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 t...Continue Reading

Citations

May 2, 2003·Expert Opinion on Investigational Drugs·Masao Endoh
Oct 6, 2009·Journal of Molecular and Cellular Cardiology·Lori A WalkerPeter M Buttrick
Apr 26, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·R M SaraivaM O Masuda
Aug 29, 2002·Journal of Cardiovascular Pharmacology·Masao Endoh

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