Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis.

Fazia Brouri, Naima Hanoun, Odile Mediani, Françoise Saurini, Michel Hamon, Paul M Vanhoutte, Philippe Lechat

Service de Pharmacologie, Hôpital de la Pitié-Salpêtrière, 47-91, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.

European journal of pharmacology 2004 Feb 6

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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 microg/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 microg/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.

Citation

Fazia Brouri, Naima Hanoun, Odile Mediani, Françoise Saurini, Michel Hamon, Paul M Vanhoutte, Philippe Lechat. Blockade of beta 1- and desensitization of beta 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. European journal of pharmacology. 2004 Feb 6;485(1-3):227-34