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Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction

Pires, María Ja,b; Rodríguez-Peña, Ana Ba; Arévalo, Miguelc; Cenador, Begoñaa; Evangelista, Stefanod; Esteller, Alejandroa; Sánchez-Rodríguez, Ángele; Colaço, Aurab; López-Novoa, José Ma

doi: 10.1097/HJH.0b013e3282efeecb
Original papers: Kidney
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Objectives D/L-Nebivolol is a lypophilic β1-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 β-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.

aInstituto Reina Sofía de Investigación Nefrológica. Departamento de Fisiología y Farmacología Universidad de Salamanca, Salamanca, Spain

bDepartamento de Ciencias Veterinarias, Universidade de Tras-os-Montes e Alto Douro, Vila Real, Portugal

cDepartamento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca, Spain

dMenarini Ricerche spa. Preclinical Development Department, Firenze, Italy

eHypertension Unit, Hospital Universitario de Salamanca, Salamanca, Spain

Received 13 December, 2006

Revised 13 June, 2007

Accepted 11 July, 2007

Correspondence to Dr José M. López-Novoa, Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Avda. Campo Charro sn. Salamanca 37007, Spain Tel: +34 923 294472; fax: +34 923 294669; e-mail: jmlnovoa@usal.es

© 2007 Lippincott Williams & Wilkins, Inc.