Signalling transduction pathways implicated in Nebivolol-induced NO production in endothelial cells

Some of vascular endothelial dysfunctions are currently caused by impairment in nitric oxide biodisponibility, involving resistance arteries and leading to increase the systemic blood pressure and thus leading to hypertension. Hence, antihypertensive agents, that reverse endothelial dysfunction and lower blood pressure, might improve the prognosis of patients with hypertension. Many studies investigated the underlying mechanism of Nebivolol (NEB)-inducing vasodilation and reported the highly role of selective β1 adrenoceptor blocker with its additional vasodilating mechanisms. However, the way that mediates these actions remains controversial. A lot of hypothesizes suggested a NO endotheliumdependent release induced by NEB in static conditions. This NO production was due to stimulation of β3 adrenoreceptors and oestrogen receptors and was dependent on e-NOS activation, then implicating PI3-K and Akt signaling pathway. Other findings reported an endothelium independent mechanism, then independent from Ca+2/Calmodulin, e-NOS and β-adrenoreceptor pathway (Fig. 1). Other ways are also described, so this paper presents an overview of the NEB signaling pathways in terms of endothelium dependence as well as the involved receptors.