title: Nebivolol ameliorates asymmetric dimethylarginine-induced vascular response in rat aorta via β3 adrenoceptor-mediated mechanism.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, induces endothelial dysfunction. Nebivolol, a highly selective β1-adrenergic receptor (AR) blocker, is the only beta-blocker known to induce vascular production of nitric oxide.
  
  
  OBJECTIVE
  The present study was designed to evaluate the effect and mechanism of nebivolol on ADMA-induced vascular response in rat aorta in vitro.
  
  
  METHODS
  In vitro, the effects of nebivolol and ADMA on resting tone or contraction induced by phenylephrine (PE, 10(-6 )mol/L) and relaxation induced by acetylcholine (Ach, 10(-10)-10(-5 )mol/L) were evaluated.
  
  
  RESULTS
  ADMA in a concentration-dependent manner increased the resting and PE-induced tone and reduced Ach-induced relaxation. Nebivolol inhibited the ADMA-induced enhancements in tone and reversed the effects of ADMA on Ach-induced relaxation. These effects of nebivolol were blocked by selective β3 receptor blocker cyanopindolol (1 μM), but not by selective β2 receptor blocker butoxamine (50 μM).
  
  
  CONCLUSIONS
  Nebivolol ameliorates the ADMA-induced vascular responses in rat aorta, at least in part, by mechanisms involving β3 adrenoceptor.
authors.affiliation: a Department of Pharmacology , Shanxi Medical University , Taiyuan, Shanxi Province , People's Republic of China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Department of General surgery , Shanxi Academy of Medical Sciences & Shanxi Dayi Hospital , Taiyuan, Shanxi Province , People's Republic of China.
authors.forename: Xiushan
authors.initials: X
authors.lastname: Dong
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology*; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D000068577:Nebivolol / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D004791:Enzyme Inhibitors; D022702:Receptors, Adrenergic, beta-3; D000068577:Nebivolol; D002078:Butoxamine; D010656:Phenylephrine; D009569:Nitric Oxide; C047975:cyanopindolol; C018524:N,N-dimethylarginine; D001120:Arginine; D010869:Pindolol; D019001:Nitric Oxide Synthase
keywords: aorta; asymmetric dimethylarginine; nebivolol; vascular response; β3 adrenoceptor