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

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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 α1A, α1B, α1D, β1, β2and β3were similar in cav‐1KO and WT. (‐)‐Noradrenaline contracted cav‐1KO (‐log EC50M=7.1) and WT (‐log EC50M=7.3) arteries through prazosin‐sensitive receptors. Maximum (‐)‐noradrenaline‐evoked contractions were greater in cav‐1KO than WT arteries. (‐)‐Isoprenaline relaxed WT arteries (‐log EC50M=7.3) more potently than cav‐1KO arteries (‐log EC50M=6.8); the effects were antagonized partially and similarly by the β2‐selective antagonist ICI118551 (50 nM). The (‐)‐isoprenaline‐evoked relaxation was partially antagonized by the β1‐adrenoceptor‐selective antagonist CGP20712 (300 nM) in WT but not cav‐1KO arteries. The β3‐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 β3‐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 α1‐ and β2‐adrenoceptors is similar in cav‐1KO and WT mice. β1‐adrenoceptor‐mediated relaxation in WT is lost in cav‐1KO and replaced by the appearance of β3‐adrenoceptors.British Journal of Pharmacology(2007)150, 261–270. doi:10.1038/sj.bjp.0706980