Nebivolol decreases oxidative stress in essential hypertensive patients and increases nitric oxide by reducing its oxidative inactivation.
OBJECTIVE
To obtain further insight into the mechanism underlying the vasodilator effect of nebivolol. Since oxidative inactivation of nitric oxide (NO) is regarded as an important cause of its decreased biological activity, we studied (1) the effect of nebivolol on some oxidative parameters in essential hypertensive patients; (2) the effect of plasma of nebivolol-treated patients on reactive oxygen species production and NO availability in endothelial cells.


METHODS
A total of 20 healthy subjects and 20 matched essential hypertensive patients treated with atenolol or nebivolol according to a double-blind, randomized design participated in the study. We measured low-density lipoprotein (LDL) and plasma hydroperoxides, 8-isoprostanes, oxidized LDL, susceptibility of LDL to oxidation (lag phase) and LDL vitamin E and the effect of plasma of nebivolol- and atenolol-treated patients on reactive oxygen species production and NO availability in endothelial cells exposed to oxidative stress.


RESULTS
In hypertensive patients, nebivolol and atenolol significantly reduced blood pressure values after 4 weeks of treatment. Plasma and LDL hydroperoxides, plasma 8-isoprostanes, plasma ox-LDL and LDL lag phase were significantly improved only in the patients receiving nebivolol compared with the atenolol group. Similarly there was a reduction of reactive oxygen species (ROS) and O2*- concentration in endothelial cells exposed to oxidative stress after incubation of the cells with plasma of the patients enrolled in the trial only in the patients receiving nebivolol compared to atenolol group. Furthermore, the reduction of basal and stimulated NO induced by oxidative stress in endothelial cells was significantly lower in the patients receiving nebivolol compared to atenolol group.


CONCLUSIONS
The findings of the present study indicate that nebivolol, through its antioxidant properties, increases NO also by decreasing its oxidative inactivation.
Fratta Pasini
Anna
A
Department of Biomedical and Surgical Sciences (Medicina D), University of Verona, Verona, Italy.
Garbin
Ulisse
U
Nava
Maria Cristina
MC
Stranieri
Chiara
C
Davoli
Anna
A
Sawamura
Tatsuya
T
Lo Cascio
Vincenzo
V
Cominacini
Luciano
L
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D001578:Benzopyrans / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000959:Antihypertensive Agents; D000975:Antioxidants; D001578:Benzopyrans; D001798:Blood Proteins; D004983:Ethanolamines; D017382:Reactive Oxygen Species; D000068577:Nebivolol; D009569:Nitric Oxide; D001262:Atenolol