Nebivolol and beta 3 mediated cardioprotection: Beta 3 adrenoceptor stimulation has been shown to have cardioprotection mediated through nitric oxide synthase which produces nitric oxide. Nebivolol has higher beta 1 selectivity than bisoprolol, carvedilol and bucindolol. Nebivolol is a vasodilatory beta blocker useful in treatment of heart failure in addition to routine uses for beta blockers. The vasodilatory property of nebivolol is probably mediated through stimulation of beta 3 receptors which in turn leads to endothelial nitric oxide synthase (eNOS) activation resulting in the release of nitric oxide. This improves endothelial function and produces peripheral vasodilatation.
Nebivolol has effect on neuronal nitric oxide synthase (nNOS) as well. The cardioprotective effect of nebivolol is abolished in experimental animals by administration of beta 3 antagonists. Nebivolol can reduce ventricular remodeling and preserve left ventricular function by beta 3 adrenoceptor mediated pathways. Nebivolol has been shown to reduce myocardial injury and mortality in mice [Zheng Zhang et al. Nebivolol Protects against Myocardial Infarction Injury via Stimulation of Beta 3-Adrenergic Receptors and Nitric Oxide Signaling. PLoS One. 2014; 9: e98179]. It also reduces the amount myocardial scar and severe fibrosis.