Toxic cardiac effects of catecholamines:: role of β-adrenoceptor downregulation

The aim of our study was to analyse the mechanisms underlying cardiac toxicity caused by beta-adrenoceptor stimulation and the relationships with their associated downregulation during heart failure. We used the experimental model of coronary artery ligation-induced myocardial infarction in male Wistar rats. In order to increase beta-adrenergic stimulation, rats were subjected to a 15-day chronic isoprenaline administration (30 mug/kg/h). Isoprenaline administration induced haemodynamic inotropic compensation, almost abolished in vitro inotropic response to isoprenaline on papillary muscle (P<0.005) but promoted fibrosis. Isoprenaline treatment markedly reduced the B-max of beta(2)-adrenoceptors (by 53% in sham and 44% in infarcted rats) but not that of beta(1)-adrenoceptors. These results suggest that beta(1)-adrenoceptors rather than beta(2)-adrenoceptors underlie the deleterious effects of chronic beta-adrenergic stimulation on cardiac fibrosis and are in agreement with the demonstrated benefit induced in human heart failure by beta(1)-adrenoceptor antagonists. (C) 2002 Elsevier Science B.V. All rights reserved.