OBJECTIVES: The objective of the present study was to elucidate the vasodilator mechanisms of nebivolol, a high selective beta(1)-receptor antagonist with antioxidant properties. BACKGROUND: Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity. METHODS: Oxidative stress was induced through the binding of oxidized (ox)-low-density lipoprotein (LDL) to its specific endothelial receptor, called "lectin-like oxidized LDL receptor-1" (LOX-1), in bovine and human endothelial cells and in Chinese hamster ovary cells stably expressing bovine LOX-1 (BLOX-1-CHO cells). Reactive oxygen species (ROS), superoxide (O(2)(*-)), and NO were measured in cells by flow cytometry. RESULTS: Nebivolol and its 4-keto derivative prevented in a dose-dependent manner the increase of ROS (p < 0.001) and O(2)(*-) (p < 0.001) in bovine aortic endothelial cells (BAECs), human umbilical vein endothelial cells (HUVECs), and BLOX-1-CHO cells stimulated with ox-LDL. Atenolol had no effect. The incubation of HUVECs and BAECs with ox-LDL reduced basal and bradykinin-induced NO and nitrite concentration (p from <0.001 to <0.01). Nebivolol and its 4-keto derivative prevented the reduction of basal and stimulated NO and nitrite concentration (p from <0.001 to <0.01) while atenolol had no effect. The preincubation of BAECs with blocking anti-LOX-1 monoclonal antibody (LOX-1 mAb) significantly counteracted the effect of ox-LDL on stimulated generation of NO (p < 0.001), but the effect was significantly lower than that of nebivolol and its 4-keto derivative alone (p < 0.01). CONCLUSIONS: In conclusion, the findings of the present study indicate that nebivolol increases NO also by decreasing its oxidative inactivation.
OBJECTIVES: The objective of the present study was to elucidate the vasodilator mechanisms of nebivolol, a high selective beta(1)-receptor antagonist with antioxidant properties. BACKGROUND: Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity. METHODS: Oxidative stress was induced through the binding of oxidized (ox)-low-density lipoprotein (LDL) to its specific endothelial receptor, called "lectin-like oxidized LDL receptor-1" (LOX-1), in bovine and human endothelial cells and in Chinese hamster ovary cells stably expressing bovineLOX-1 (BLOX-1-CHO cells). Reactive oxygen species (ROS), superoxide (O(2)(*-)), and NO were measured in cells by flow cytometry. RESULTS:Nebivolol and its 4-keto derivative prevented in a dose-dependent manner the increase of ROS (p < 0.001) and O(2)(*-) (p < 0.001) in bovine aortic endothelial cells (BAECs), human umbilical vein endothelial cells (HUVECs), and BLOX-1-CHO cells stimulated with ox-LDL. Atenolol had no effect. The incubation of HUVECs and BAECs with ox-LDL reduced basal and bradykinin-induced NO and nitrite concentration (p from <0.001 to <0.01). Nebivolol and its 4-keto derivative prevented the reduction of basal and stimulated NO and nitrite concentration (p from <0.001 to <0.01) while atenolol had no effect. The preincubation of BAECs with blocking anti-LOX-1 monoclonal antibody (LOX-1 mAb) significantly counteracted the effect of ox-LDL on stimulated generation of NO (p < 0.001), but the effect was significantly lower than that of nebivolol and its 4-keto derivative alone (p < 0.01). CONCLUSIONS: In conclusion, the findings of the present study indicate that nebivolol increases NO also by decreasing its oxidative inactivation.
Authors: Ricardo Carnicer; Mark J Crabtree; Vidhya Sivakumaran; Barbara Casadei; David A Kass Journal: Antioxid Redox Signal Date: 2012-09-20 Impact factor: 8.401
Authors: Robert B Neuman; Salim S Hayek; Joseph C Poole; Ayaz Rahman; Vivek Menon; Nino Kavtaradze; David Polhemus; Emir Veledar; David J Lefer; Arshed A Quyyumi Journal: J Clin Hypertens (Greenwich) Date: 2015-08-19 Impact factor: 3.738