Nebivolol ameliorates asymmetric dimethylarginine-induced vascular response in rat aorta via beta(3) adrenoceptor-mediated mechanism

摘要

Background: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, induces endothelial dysfunction. Nebivolol, a highly selective beta(1)-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 beta(3) receptor blocker cyanopindolol (1 mu M), but not by selective beta(2) receptor blocker butoxamine (50 mu M). Conclusions: Nebivolol ameliorates the ADMA-induced vascular responses in rat aorta, at least in part, by mechanisms involving beta(3) adrenoceptor.