Effect of carvedilol and nebivolol on oxidative stress-related parameters and endothelial function in patients with essential hypertension.
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 ( NO₂) - 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 NO₂ 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 NO₂ concentration. Further studies are needed to determine the molecular mechanism of these effects.
Molecular and Clinical Pharmacology Program, Faculty of Medicine, Biomedical Sciences Institute, Universidad de Chile, Santiago, Chile. rzepeda@ciq.uchile.cl
Ramiro J
RJ
Zepeda
Rodrigo
R
Castillo
Ramón
R
Rodrigo
Juan C
JC
Prieto
Ivonne
I
Aramburu
Solange
S
Brugere
Katia
K
Galdames
Viviana
V
Noriega
Hugo F
HF
Miranda
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000975:Antioxidants / Q000032:analysis; D001578:Benzopyrans / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000075222:Essential Hypertension; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D000975:Antioxidants; D001578:Benzopyrans; D002227:Carbazoles; D004983:Ethanolamines; D011412:Propanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D000077261:Carvedilol; D009569:Nitric Oxide; D005978:Glutathione