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Nebivolol may counter ADMA effects in vitro; leaves open any clinical relevance in endothelial dysfunction.
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.
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Wang et al. (2016) studied this question.
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