Canadian Science Publishing, Canadian Journal of Physiology and Pharmacology, 10(91), p. 791-796
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In porcine coronary arteries (PCAs), celiprolol, a selective β1-adrenoceptors antagonist, induces vasodilatation by an endothelium- and nitric oxide (NO)-dependent pathway. However, the mechanisms of that vascular effect have not been precisely established. β3-Adrenoceptors have been shown to be involved in the relaxation per se of various vascular beds, including coronary vessels. Thus, we evaluated (i) the presence of β3-adrenoceptors in the PCA and (ii) their role in celiprolol-induced vasodilatation. PCA rings were placed in organ baths and preconstricted with KCl. All experiments were performed in the presence of nadolol (a β1/β2-adrenoceptor antagonist). Cumulative concentration–response curves to SR 58611A and ICI 215001 (2 β3-adrenoceptor agonists) and to celiprolol were constructed. We also used semiquantitative reverse transcription – polymerase chain reaction, which clearly showed the presence of β3-adrenoceptor transcripts. SR 58611A, ICI 215001, and celiprolol induced concentration-dependent relaxations in PCA rings. SR 58611A-induced relaxation was almost abolished after removal of endothelium or pretreatment with L-NAME (a NO synthase inhibitor). The vasorelaxations induced by SR 58611A and celiprolol were inhibited in the presence of SR 59230A and L-748337 (2 selective β3-adrenoceptor antagonists). We showed (i) that PCAs possess functional β3-adrenoceptors mediating endothelium- and NO-dependent relaxation, and (ii) that celiprolol exerts a β3-adrenoceptor agonistic activity in this vascular bed.