Preventive effect of nebivolol on contrast-induced nephropathy in rats

Nephrol Dial Transplant. 2008 Mar;23(3):853-9. doi: 10.1093/ndt/gfm691. Epub 2007 Oct 12.

Abstract

Background: Altered renal vasodilatation and oxidative stress are important mechanisms of contrast-induced nephropathy (CIN). The aim of the present study was to assess the effect of nebivolol, a beta blocker, on prevention of CIN. We hypothesized that nebivolol may prevent CIN due to its renal vasodilatation and antioxidant effects.

Methods: Thirty-two Wistar-albino rats were divided into four groups (n = 8 each): control (C), contrast media (CM), nebivolol (N), and nebivolol + contrast media (NCM). CIN was induced by administration of intravenous high-osmolar contrast media diatrizoate (6 ml/kg) after 72 h of dehydration. Nebivolol (2 mg/kg) was given internally once daily for 5 days. Kidney function parameters, nitric oxide metabolites and oxidative stress markers were measured. Kidneys were excised for pathological evaluation.

Results: The decrease of creatinine clearance was 0.180 +/- 0.11 mg/dl in CM, and 0.030 +/- 0.10 mg/dl in NCM (P = 0.01). Microproteinuria was ameliorated using nebivolol (P = 0.001). Serum protein carbonyl content, malonyldialdehyde and kidney thiobarbituric acid-reacting substances levels were higher in CM than in C (P = 0.003, P < 0.001 and P = 0.034, respectively) and serum thiol was lower in CM than in C (P = 0.001). However, oxidative stress markers were similar in NCM and C. Diatrizoate decreased kidney nitrite levels, but nebivolol increased them (P = 0.027). Nebivolol attenuated the tubular necrosis, proteinaceous casts and medullary congestion, although significant protective effects, were observed in tubular necrosis (P = 0.001) and proteinaceous cast (P < 0.001).

Conclusion: This study demonstrated the protective role of nebivolol against CIN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Animals
  • Benzopyrans / pharmacology
  • Benzopyrans / therapeutic use*
  • Contrast Media / adverse effects*
  • Creatinine / blood
  • Disease Models, Animal
  • Ethanolamines / pharmacology
  • Ethanolamines / therapeutic use*
  • Female
  • Kidney / blood supply
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Malondialdehyde / blood
  • Nebivolol
  • Nitrites / metabolism
  • Oxidative Stress / drug effects
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Vasodilation / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Benzopyrans
  • Contrast Media
  • Ethanolamines
  • Nitrites
  • Thiobarbituric Acid Reactive Substances
  • Nebivolol
  • Malondialdehyde
  • Creatinine