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Nephrol Dial Transplant. 2012 Mar;27(3):913-20. doi: 10.1093/ndt/gfr449. Epub 2011 Aug 19.

Protective actions of nebivolol on chronic nitric oxide synthase inhibition-induced hypertension and chronic kidney disease in the rat: a comparison with angiotensin II receptor blockade.

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  • 1Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.



Nitric oxide (NO) deficiency contributes to chronic kidney disease (CKD) progression and hypertension. The β-blocker, nebivolol (N), also enhances NO production, and we studied whether N attenuates CKD and hypertension caused by chronic NO synthase inhibition (CNOSI).


Male Sprague-Dawley rats on 6 weeks of CNOSI (L-NAME, 150 mg/L drinking water) received placebo (P), N (10 mg/kg/day), olmesartan (O, 2.5 mg/kg/day) or N + O. Blood pressure (BP) and urine protein and NOx (metabolites of NO) were monitored throughout. We measured glomerular sclerosis (GS), creatinine clearance (C(Cr)) and components of the NO and oxidant pathways in the renal cortex.


BP increased >50 mmHg in P by weeks 4-6, but no change occurred in N, O or N + O. P rats developed proteinuria and GS and C(Cr) was ∼30% of normal. In N, O and N + O, all values remained normal. In renal cortex of P, p22phox and nitrotyrosine abundance as well as H(2)O(2) levels were higher and extracellular superoxide dismutase (EC SOD) was lower versus normal kidneys. N, O and N + O normalized p22phox, H(2)O(2) and EC SOD and increased Mn SOD above normal. The cortical neuronal NO synthase (nNOS) β abundance increased in P and this was prevented by N, O and N + O.


We suggest that the major benefit from both N and O is reduction in oxidative stress in the renal cortex, which may potentiate residual local NO. There was no additive benefit of N + O since each drug effectively prevented injury, but a combination may be beneficial where protection is incomplete with each drug. The increased nNOSβ protein seen early in the course of the CKD may contribute to the evolving GS.

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