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Updated: Sep 28, 2026

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice
Published on: October 3, 2019
Toxic cardiac effects of catecholamines: role of beta-adrenoceptor downregulation
Fazia Brouri1, Laurent Findji, Odile Mediani
1Service de Pharmacologie, Hôpital de la Pitié-Salpêtrière, Paris, France.
Abstract:
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 microg/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.
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