title: 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.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA. nmoningk@ufl.edu
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Moningka
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Tsarova
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sasser
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000627:therapeutic use*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068577:Nebivolol; D009569:Nitric Oxide; C437965:olmesartan; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester