Blockade of β1- and desensitization of β 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis

Abstract

The aim of the present study was to analyse the role of β 1- and β2-adrenoceptors in the catecholamine-induced myocardial remodeling, especially the interstitial fibrosis. Wistar rats were subjected to a 2-week chronic isoprenaline administration (30 μg/kg/h). Rats received a concomitant treatment with the selective β1- adrenoceptor antagonist, bisoprolol (50 mg/kg/day p.o.) or were chronically pretreated with the selective β2-adrenoceptor agonist salbutamol (40 μg/kg/h) for 1 week to induce β2-adrenoceptor desensitization. The pretreatment with salbutamol induced a 59% down-regulation of left ventricular β2-adrenoceptors compared to control. The extent of the isoprenaline-induced left ventricular fibrosis was significantly reduced in both the bisoprolol and salbutamol groups compared with the control isoprenaline-treated group especially in the apical region (1.7±0.6% and 1.4±0.3% versus 6.0±1.3%, respectively, P<0.005). β 1-adrenoceptor blockade and β2-adrenoceptors down-regulation provided similar protection against isoprenaline-induced cardiac interstitial fibrosis suggesting that both β-adrenoceptors are involved in such cardiac remodeling process. © 2003 Elsevier B.V. All rights reserved.