title: Celiprolol induces β(3)-adrenoceptors-dependent relaxation in isolated porcine coronary arteries.
abstract: In porcine coronary arteries (PCAs), celiprolol, a selective β(1)-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. β(3)-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 β(3)-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 β(1)/β(2)-adrenoceptor antagonist). Cumulative concentration-response curves to SR 58611A and ICI 215001 (2 β(3)-adrenoceptor agonists) and to celiprolol were constructed. We also used semiquantitative reverse transcription - polymerase chain reaction, which clearly showed the presence of β(3)-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 β(3)-adrenoceptor antagonists). We showed (i) that PCAs possess functional β(3)-adrenoceptors mediating endothelium- and NO-dependent relaxation, and (ii) that celiprolol exerts a β(3)-adrenoceptor agonistic activity in this vascular bed.
authors.affiliation: a L'Université Nantes Angers Le Mans (LUNAM) - Oniris, UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle, Atlanpole-La Chantrerie, B.P. 40706, Nantes F-44307, France.
authors.forename: Mohammed Amine
authors.initials: MA
authors.lastname: Abdelkrim
authors.forename: Lionel
authors.initials: L
authors.lastname: Martignat
authors.forename: Marc
authors.initials: M
authors.lastname: Gogny
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Desfontis
authors.forename: Jacques
authors.initials: J
authors.lastname: Noireaud
authors.forename: Mohamed Yassine
authors.initials: MY
authors.lastname: Mallem
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017272:Celiprolol / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D014665:Vasodilator Agents; D009569:Nitric Oxide; D017272:Celiprolol; D019001:Nitric Oxide Synthase