Salt-induced renal injury in spontaneously hypertensive rats: effects of nebivolol

Am J Nephrol. 2010;32(6):557-66. doi: 10.1159/000321471. Epub 2010 Nov 2.

Abstract

Background: we investigated renal effects of nebivolol, a selective β(1)-receptor blocker with additional antioxidative ability, in spontaneously hypertensive rats (SHR) where increased salt intake induces oxidative stress and worsens renal function as a result of further activation of the renin-angiotensin and sympathetic nervous systems.

Methods: male SHR were given an 8% salt diet (HS; n = 22) for 5 weeks; their age-matched controls (n = 9) received standard chow. Nebivolol was given at a dose of 10 mg/kg/day for 5 weeks in 11 HS rats.

Results: HS increased blood pressure, plasma renin concentration, urinary protein excretion, and renal nitroxidative stress while decreasing renal blood flow and angiotensin 1-7 receptor (mas) protein expression. There was no change in angiotensin II type 1 receptor expression among the experimental groups. Nebivolol did not alter the salt-induced increase in blood pressure but reduced urinary protein excretion, plasma renin concentration, and nitroxidative stress. Nebivolol also increased neuronal NOS expression while preventing the salt-induced decrease in renal blood flow and mas protein expression.

Conclusion: nebivolol prevented salt-induced kidney injury and associated proteinuria in SHR through a blood pressure-independent mechanism. Its protective effects may be related to reduction in oxidative stress, increases in neuronal NOS and restoration of angiotensin II type 1/mas receptor balance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / prevention & control
  • Adrenergic beta-1 Receptor Antagonists / administration & dosage
  • Adrenergic beta-1 Receptor Antagonists / pharmacology*
  • Analysis of Variance
  • Angiotensin II / metabolism
  • Animals
  • Benzopyrans / administration & dosage
  • Benzopyrans / pharmacology*
  • Blood Pressure / drug effects
  • Ethanolamines / administration & dosage
  • Ethanolamines / pharmacology*
  • Male
  • Nebivolol
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / drug effects
  • Proteinuria
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Rats, Inbred SHR
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Renal Circulation / drug effects
  • Renin / blood
  • Renin-Angiotensin System / drug effects*
  • Sodium Chloride / adverse effects*

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Benzopyrans
  • Ethanolamines
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • Nebivolol
  • Angiotensin II
  • Sodium Chloride
  • Nitric Oxide Synthase
  • Renin