Beta 3 adrenoceptors are cardioprotective

Beta 3 adrenoceptors are cardioprotective

Beta 3 adrenoceptors were described way back in 1980. They increase lipolysis, oxidation of fats, expenditure of energy and the action of insulin. Hence they have been thought to be important target for the treatment of diabetes mellitus and obesity [1].

Cardioprotective action of beta 3 adrenoceptors

Beta 3 adrenoceptors are stimulated only at high concentration of catecholamines, inducing negative inotropic effect and act as protection from overstimulation by catecholamines [2]. Thus beta 3 adrenoceptors are rather antagonistic to beta 1 and beta 2 adrenoceptors. Initially it was thought that beta 3 adrenoceptors act by release of nitric oxide through the endothelial nitric oxide synthase (eNOS) pathway.

Later it has been shown that other nitric oxide synthases were also involved in the release of nitric oxide by beta 3 adrenoceptor stimulation, namely inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). There is also experimental evidence that beta 3 adrenoceptor activation by an agonist protects against myocardial infarction injury by activation of eNOS and nNOS [3].

Nebivolol and beta 3 mediated cardioprotection

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 activation resulting in the release of nitric oxide. This improves endothelial function and produces peripheral vasodilatation.

Nebivolol has effect on neuronal nitric oxide synthase 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 [4]. It also reduces the amount myocardial scar and severe fibrosis.

References

1. de Souza CJ et al. Beta 3-adrenoceptor agonists as anti-diabetic and anti-obesity drugs in humans. Curr Pharm Des. 2001;7:1433-49.
2. Xiaolin Niu et al, Cardioprotective Effect of Beta-3 Adrenergic Receptor Agonism. Role of Neuronal Nitric Oxide Synthase.J Am Coll Cardiol, 2012; 59:1979-1987.
3. Niu X et al. β3-adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation. PLoS One. 2014;9:e98713.
4. Zhang Z, Ding L, Jin Z, Gao G, Li H, Zhang L, Zhang L, Lu X, Hu L, Lu B, Yu X, Hu T. Nebivolol Protects against Myocardial Infarction Injury via Stimulation of Beta 3-Adrenergic Receptors and Nitric Oxide Signaling. PLoS One. 2014; 9: e98179.