The function of α- and β-adrenoceptors of the saphenous artery in caveolin-1 knockout and wild-type mice

Abstract

Background and purpose: Adrenoceptors can associate with cardiac caveolae. To investigate the function of vascular caveolae, adrenoceptor-mediated effects were compared in the saphenous artery of caveolin-1 knockout (cav-1KO) and wild-type (WT) mice. Experimental approach: Electronmicroscopy was used to detect caveolae. Real-Time quantitative PCR was used for adrenoceptor subtypes. Catecholamine-evoked contractions and relaxations were studied in arterial segments. Key results: Caveolae were found in arterial smooth muscle from WT but not from cav-1KO mice. Arterial mRNA levels for the adrenoceptors α 1A, α 1B, α 1D, β 1, β 2 and β 3 were similar in cav-1KO and WT. (-)-Noradrenaline contracted cav-1KO (-log EC 50M=7.1) and WT (-log EC 50M=7.3) arteries through prazosin-sensitive receptors. Maximum (-)-noradrenaline-evoked contractions were greater in cav-1KO than WT arteries. (-)-Isoprenaline relaxed WT arteries (-log EC 50M=7.3) more potently than cav-1KO arteries (-log EC 50M=6.8); the effects were antagonized partially and similarly by the β 2-selective antagonist ICI118551 (50 nM). The (-)-isoprenaline-evoked relaxation was partially antagonized by the β 1-adrenoceptor-selective antagonist CGP20712 (300 nM) in WT but not cav-1KO arteries. The β 3-adrenoceptor-selective antagonist L748337 (100nM) partially antagonized the relaxant effects of (-)-isoprenaline in cav-1KO but not in WT arteries. BRL37344 partially relaxed arteries through β 3-adrenoceptors in cav-1KO but not WT. The relaxant effects of BRL37344 were decreased by the NO synthase inhibitor ΩL-nitroarginine. Conclusions and implications: The function of arterial α 1- and β 2-adrenoceptors is similar in cav-1KO and WT mice. β 1-adrenoceptor-mediated relaxation in WT is lost in cav-1KO and replaced by the appearance of β 3-adrenoceptors. © 2007 Nature Publishing Group All rights reserved.