Nebivolol Increases Nitric Oxide Synthase via β3 Adrenergic Receptor in Endothelial Cells Following Exposure to Plasma from Preeclamptic Patients

Abstract

Background: Low bioavailability of nitric oxide (NO) is related to the pathophysiology of preeclampsia (PE). In the present study, we investigated the effect of nebivolol (NEB), a β3-receptor agonist with vasodilator properties, on the NO synthesis in endothelial cells incubated with plasma from preeclamptic patients. Methods and results: Human umbilical vein endothelial cells (HUVECs) were incubated with plasma from healthy pregnant (HP) and PE women; NO quantification was assessed by a fluorescence compound. We found that endothelial cells incubated with plasma from women with PE show lower NO levels compared with the HP group (p < 0.0001). However, NEB treatment increases NO levels, partially, mediated by β3 adrenergic receptors (p < 0.0001) and through eNOS activation (p < 0.0001). Conclusions: Our results suggest that NEB acts in NO synthesis through eNOS activation and β3 adrenergic receptors in the endothelium. However, further studies will be needed to understand this molecule.

Fetoplacental vascular effects of maternal adrenergic antihypertensive and cardioprotective medications in pregnancy

“…Endothelial factors, including nitric oxide, PGI2, H2S and EDHF, are well known to evoke vasorelaxation, whereas the production of ET-1, TXA2 or VSMC depolarization causes vasoconstriction [10]. Figure 4 summarizes the major mechanisms initiated by the activation of adrenergic receptors in the endothelium and in the VSMC layer of resistance-size vessels in animal models, and in the human fetoplacental vasculature [94–131].…”

Multitargeting in cardioprotection: An example of biaromatic compounds

“…[228] Though nebivolol has a much lower affinity for β3than for β1or β2-ARs (pK i [β3] = 5.6 vs. pK i [β1] = 9.17 and pK i [β2] = 7.96) [229] the direct binding of nebivolol to the β3-receptor remains one of the most attractive concepts that explains its specific endothelial vasodilation. [230][231][232][233] The effects of nebivolol on the vascular system, which are attributed to the eNOS enzyme, were observed in humans. It was found that nebivolol had direct endothelium-dependent vasodilation effects and increased the reactivity to stimuli such as hyperemia in both the arterial and venous circulation.…”

“…Though nebivolol has a much lower affinity for β3‐ than for β1‐ or β2‐ARs ( pK i [β3] = 5.6 vs. pK i [β1] = 9.17 and pK i [β2] = 7.96) [ 229 ] the direct binding of nebivolol to the β3‐receptor remains one of the most attractive concepts that explains its specific endothelial vasodilation. [ 230–233 ]…”