Effects of thiol antioxidant on Reduced Nicotinamide Adenine Dinucleotide Phosphate oxidase in hypertensive Dahl salt-sensitive rats

Ling Zhang, Shigemoto Fujii, Junsuke Igarashi, Hiroaki Kosaka

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent studies implicate of reactive oxygen species (ROS) in hypertension; however, whether reactive oxygen species promote hypertensive derangements is not fully clear. We thus investigated the effects of an antioxidant, n-acetyl-l-cysteine, on hypertensive Dahl salt-sensitive rats. High-salt intake for 4 weeks markedly elevated systolic arterial pressure, urinary excretion of protein, 8-isoprostane, and H 2O 2, and the enzyme activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with the elevated expression of its subunits gp91phox and p47phox at the levels of mRNA and protein. Supplement with n-acetyl-l-cysteine reduced the increase in systolic arterial pressure and counteracted the elevation of urinary excretion of protein, 8-isoprostane, and H 2O 2, and the increases in NADPH oxidase activity/expression in high-salt-loaded Dahl salt-sensitive rats. n-acetyl-l-cysteine supplement ameliorated plasma and urinary levels of thromboxane B 2 (an end metabolite of thromboxane A 2), associated with improvement of both the abnormal contraction and the impaired nitric oxide-dependent relaxation in renal arteries. These results revealed that oxidative stress mediates hypertensive changes in Dahl salt-sensitive rats, because thiol antioxidant n-acetyl-l-cysteine attenuated the augmentation of local ROS production by diminishing the elevation of NADPH oxidase expression and ameliorated renal/vascular hypertensive changes.

Original languageEnglish
Pages (from-to)1813-1820
Number of pages8
JournalFree Radical Biology and Medicine
Volume37
Issue number11
DOIs
Publication statusPublished - 2004 Dec 1

Keywords

  • Dahl
  • Free radicals
  • Hydrogen peroxide
  • NAC
  • NADPH oxidase
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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