Diminished responsiveness to cardiac beta 1-adrenoceptor agonists in rats with chronic heart failure following myocardial infarction.
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 to denopamine is diminished in the CHF rat and this alteration is accounted for, in part, by a decrease in cardiac beta-adrenoceptor density.
Sanbe
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A
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Takeo
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S
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D004247:DNA / Q000032:analysis / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D018342:Receptors, Adrenergic, beta-1; D004247:DNA; D007545:Isoproterenol; C037293:denopamine