Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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.

The aim of our study was to analyse the mechanisms underlying cardiac toxicity caused by β-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 β-adrenergic stimulation, rats were subjected to a 15-day chronic isoprenaline administration (30 μg/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 Bmax of β2-adrenoceptors (by 53% in sham and 44% in infarcted rats) but not that of β1-adrenoceptors. These results suggest that β1-adrenoceptors rather than β2-adrenoceptors underlie the deleterious effects of chronic β-adrenergic stimulation on cardiac fibrosis and are in agreement with the demonstrated benefit induced in human heart failure by β1-adrenoceptor antagonists.