Effect of Carvedilol and Nebivolol on Oxidative Stress‐related Parameters and Endothelial Function in Patients with Essential Hypertension

Abstract

Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 and 75 years of age, with mild-to-moderate EH complications. Participants were randomized to receive either carvedilol (12.5 mg) (n = 23) or nebivolol (5 mg) (n = 21) for 12 weeks. Measurements included; 24-hr ambulatory blood pressure (BP), flow-mediated dilatation, levels of nitric oxide estimated as nitrite -a nitric oxide metabolite (NO 2 ) -in plasma, and oxidative stress-related parameters in plasma and erythrocyte. EH patients who were treated with nebivolol or carvedilol showed systolic BP reductions of 17.4 and 19.9 mmHg, respectively, compared with baseline values (p < 0.01). Diastolic BP was reduced by 13.7 and 12.8 mmHg after the treatment with ebivolol and carvedilol, respectively (p < 0.01) ( fig. 2B). Nebivolol and carvedilol showed 7.3% and 8.1% higher endothelium-dependent dilatation in relation to baseline values (p < 0.05). Ferric-reducing ability of plasma (FRAP) and reduced glutathione/oxidized glutathione (GSSH) ratio showed 31.5% and 29.6% higher levels in the carvedilol group compared with basal values; however, nebivolol-treated patients did not show significant differences after treatment. On the other hand, the NO 2 plasma concentration was not modified by the administration of carvedilol. However, nebivolol enhanced these levels in 62.1% after the treatment. In conclusion, this study demonstrated the antihypertensive effect of both beta-blockers. However, carvedilol could mediate these effects by an increase in antioxidant capacity and nebivolol through the raise in NO 2 concentration. Further studies are needed to determine the molecular mechanism of these effects.

Effect of Nebivolol on Endothelial Dysfunction in Coronary Artery Disease Patients -An Open Label Randomized Controlled Clinical Trial (NEDCAD)

“…In hypertensive patients, treatment with Nebivolol for 12 weeks did not improve the total antioxidant status as compared to carvedilol. 11 Although the patients in our group had coronary artery disease and hypertension, these findings are in support of our data. On contrary, Nebivolol given for eight months in patients with heart failure and diabetes, showed a significant improvement in antioxidant protection as assessed by increase in SH group level.…”

Dual targeting of TNF-αand free radical toxic stress as a promising strategy to manage experimental polycystic ovary

“…Although the exact mechanism of carvedilol beneficial effects has not been fully understood, it seems that carvedilol exerts its effect through OS markers normalization (lipid peroxides, nitric oxide, and protein thiols) and lowers the release of inflammatory cytokines such as TNF-a, interleukin-6 (IL-6), and eicosanoids (Arab & El-Sawalhi, 2013), suggesting its beneficial effects in hyper-inflammation (Mizuochi et al, 2007) and reducing OS (Oettl et al, 2001;Ouyang et al, 2013;Zepeda et al, 2012). The hydroxylated compounds of SB 211475, BM 910228, and SB 209995 as carvedilol's main metabolites exert the greatest antioxidant activity, which may be responsible for carvedilol protective effect (Lysko et al, 2000).…”

Influence of beta-blockers on endothelial function: A meta-analysis of randomized controlled trials

“…A forest plot illustrating the comparison between 3 rd and 2 nd generation of beta-blockers is shown in Figure 2B. In addition to a 3 rd and 2 nd generation comparison, Zepeda et al [14] also compared with each other the effects of two 3 rd generation beta-blockers: carvedilol and nebivolol. The two agents gave a similar improvement of FMD, with a MD of: 3.75 ± 8.67 for carvedilol and 4.7 ± Figure 2.…”

“…In 12 studies, the cuff was placed on the forearm and in 3 studies measurements was performed with cuff placed on the arm [10][11][12]. Six studies reported the number of observers who assessed FMD [9,10,[13][14][15][16]. In 5 of those studies, only 1 person was responsible for the FMD measurements.…”