Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Positive influence of AT(1) receptor antagonism upon the impaired celiprolol-induced vasodilatation in aorta from spontaneously hypertensive rats

Abstract :

We evaluated celiprolol-induced vasodilatation in aorta taken from 12-week-old spontaneously hypertensive rats (SHR) and the effect of AT(1) angiotensin II receptor antagonism on the vasodilatory action of celiprolol in Wistar Kyoto (WKY) rats and SHR. In WKY rats, the celiprolol-induced relaxation was greatly decreased in denuded aorta, and completely abolished in intact aorta by Nω-nitro-l-arginine methyl ester (⌊-NAME, 100 microM). In SHR, celiprolol-induced relaxation was reduced compared to WKY rats (Emax (value obtained for the highest concentration, 300 µM)=39.1+ or - 3.78%, n=21 vs. 80.4 + or - 3% in WKY rats, n=10; P<0.0001). Endothelium removal or pre-treatment with ⌊-NAME did not alter celiprolol-induced relaxation in SHR. In both strains, relaxation to celiprolol was decreased in the presence of nadolol (a β12-adrenoceptor antagonist, 10 µM). N-[[3-[(2S)-2-hydroxy-3-[[2-[4-[(phenylsulfonyl)amino] phenyl]ethyl]amino] propoxy]phenyl]methyl]-acetamide (L748337, a β3-adrenoceptor antagonist, 7 µM) had no effect. A 12-day treatment with candesartan cilexetil (an AT(1) receptor antagonist, 0.37 or 1mg/kg/day) reduced systolic blood pressure in both strains, but only improved relaxation to celiprolol in SHR, and only at the highest dose (Emax=64.2+/-3.9%, n=10, P<0.0001 vs. SHR control). In both strains, local aortic AT1 receptor antagonism with candesartan CV11974 (100 µM) had no effect. The endothelial β12 relaxation induced by celiprolol was therefore impaired in SHR aorta and AT1 receptor antagonism improved the response to celiprolol, in conjunction with a reduction in blood pressure. This work highlights the need to analyse the potential benefit of a combination of celiprolol/AT1 receptor antagonist in the treatment of hypertension.

Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-angers.fr/hal-03275803
Contributeur : Okina Université d'Angers <>
Soumis le : jeudi 1 juillet 2021 - 14:07:28
Dernière modification le : vendredi 2 juillet 2021 - 03:44:07

Identifiants

Collections

Citation

Frédérique Sauvaget, Mohamed Yassine Mallem, Véronique Bucas, Marc Gogny, Jean-Claude Desfontis, et al.. Positive influence of AT(1) receptor antagonism upon the impaired celiprolol-induced vasodilatation in aorta from spontaneously hypertensive rats. European Journal of Pharmacology, 2010, 644 (1-3), pp.169 - 175. ⟨10.1016/j.ejphar.2010.07.003⟩. ⟨hal-03275803⟩

Partager

Métriques

Consultations de la notice

6