Blockade of beta 1- and desensitization of beta 2-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 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.
Brouri
Fazia
F
Service de Pharmacologie, Hôpital de la Pitié-Salpêtrière, 47-91, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
Hanoun
Naima
N
Mediani
Odile
O
Saurini
Françoise
F
Hamon
Michel
M
Vanhoutte
Paul M
PM
Lechat
Philippe
P
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism* / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D000420:Albuterol