Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction.
OBJECTIVE
D/L-Nebivolol is a lypophilic beta1-adrenergic antagonist which is devoid of intrinsic sympathomimetic activity and can increase nitric oxide (NO) bioavailability with its subsequent vasodilating properties. The purpose of the present work was to assess the effect of long-term nebivolol administration on both renal damage and endothelial dysfunction induced by renal mass reduction (RMR) in rats. Atenolol, which does not increase NO bioavailability, was included in the study as a comparative beta-adrenoceptor antagonist.


METHODS
Rats were subjected to both right nephrectomy and surgical removal of two-thirds of the left kidney in order to retain approximately one-sixth of the total renal mass. One week after ablation, rats were distributed randomly according to the following experimental groups: control group containing RMR rats without treatment; RMR rats treated daily with nebivolol for 6 months (drinking water, 8 mg/kg per day); and RMR rats treated daily with atenolol for 6 months (drinking water, 80 mg/kg per day). A group of sham-operated animals was also included.


RESULTS
Administration of either nebivolol or atenolol similarly reduced arterial pressure in comparison with RMR untreated animals; however, animals receiving nebivolol presented lower levels of collagen type I expression as well as lower glomerular and interstitial fibrosis than those receiving atenolol. Urinary excretion of oxidative stress markers were also lower in animals receiving nebivolol than in rats treated with atenolol. Furthermore, nebivolol prevented RMR-induced endothelial dysfunction more efficiently than atenolol.


CONCLUSIONS
Nebivolol protects against renal fibrosis, oxidative stress and endothelial dysfunction better than equivalent doses, in terms of arterial pressure reduction, of atenolol in a hypertensive model of renal damage induced by RMR.
Pires
María J
MJ
Instituto Reina Sofía de Investigación Nefrológica. Departamento de Fisiología y Farmacología Universidad de Salamanca, Salamanca, Spain.
Rodríguez-Peña
Ana B
AB
Arévalo
Miguel
M
Cenador
Begoña
B
Evangelista
Stefano
S
Esteller
Alejandro
A
Sánchez-Rodríguez
Angel
A
Colaço
Aura
A
López-Novoa
José M
JM
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004983:Ethanolamines / Q000008:administration & dosage*; D005355:Fibrosis; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D000068577:Nebivolol; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D017392:Thiobarbituric Acid Reactive Substances; D000068577:Nebivolol; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost