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

European Journal of Pharmacology
Frédérique SauvagetJacques Noireaud

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 N(omega)-nitro-l-arginine methyl ester (l-NAME, 100 microM). In SHR, celiprolol-induced relaxation was reduced compared to WKY rats (E(max) (value obtained for the highest concentration, 300 microM)=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 l-NAME did not alter celiprolol-induced relaxation in SHR. In both strains, relaxation to celiprolol was decreased in the presence of nadolol (a beta(1)/beta(2)-adrenoceptor antagonist, 10 microM). N-[[3-[(2S)-2-hydroxy-3-[[2-[4-[(phenylsulfonyl)amino] phenyl]ethyl]amino] propoxy]phenyl]methyl]-acetamide (L748337, a beta(3)-adrenoceptor antagonist, 7 microM) 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...Continue Reading

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Citations

Oct 23, 2013·Canadian Journal of Physiology and Pharmacology·Mohammed Amine AbdelkrimMohamed Yassine Mallem
Apr 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yean Chun LohMun Fei Yam

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