Blockade of β1- and desensitization of β2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis

The aim of the present study was to analyse the role of beta(1)- and beta(2)-adrenoceptors in the catecholamine-induced myocardial remodeling, especially the interstitial fibrosis. Wistar rats were subjected to a 2-week chronic isoprenaline administration (30 mug/kg/h). Rats received a concomitant treatment with the selective beta(1)-adrenoceptor antagonist, bisoprolol (50 mg/kg/day p.o.) or were chronically pretreated with the selective beta(2)-adrenoceptor agonist salbutamol (40 mug/kg/h) for 1 week to induce beta(2)-adrenoceptor desensitization. The pretreatment with salbutamol induced a 59% down-regulation of left ventricular beta(2)-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). beta(1)-adrenoceptor blockade and beta(2)-adrenoceptors down-regulation provided similar protection against isoprenaline-induced cardiac interstitial fibrosis suggesting that both beta-adrenoceptors are involved in such cardiac remodeling process. (C) 2003 Elsevier B.V. All rights reserved.