Beneficial effects of antioxidant vitamins on the stenotic kidney

Alejandro R. Chade, Martin Rodriguez-Porcel, Joerg Herrmann, James D. Krier, Xiangyang Zhu, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Renal artery stenosis (RAS) may lead to renal injury, partly mediated through increased oxidative stress. However, the potential effects of chronic oral antioxidant intervention on the stenotic kidney remain unknown. This study was designed to test the hypothesis that chronic antioxidant vitamin supplementation in RAS would preserve renal function and structure. Single-kidney hemodynamics and function were quantified in vivo in pigs using electron-beam CT after 12 weeks of unilateral RAS (n=7), a similar degree of RAS orally supplemented with vitamins C (1 g) and E (100 IU/kg) (RAS+Vitamins, n=7), or controls (normal, n=7). Renal tissue was studied ex vivo using Western blotting and immunohistochemistry. Mean arterial pressure was similarly elevated in both RAS groups, while ischemic renal volume and glomerular filtration rate were similarly reduced. Renal blood flow was decreased in RAS compared with normal (326.5±99.9 versus 553.4±48.7 mL/min, respectively, P=0.01), but preserved in RAS+Vitamins (485.2±104.1 mL/min, P=0.3 versus normal). The marked increase in the expression of the NADPH-oxidase subunits p47phox and p67phox, nitrotyrosine, endothelial and inducible nitric oxide synthase, and nuclear factor-κB observed in RAS (P<0.05 versus normal) was normalized in RAS+Vitamins (P>0.1). Furthermore, trichrome staining and the expression of transforming growth factor-β and tissue inhibitor of matrix-metalloproteinase-1 were also decreased in RAS+Vitamins. In conclusion, chronic blockade of the oxidative stress pathway in RAS using antioxidant vitamins improved renal hemodynamics and decreased oxidative stress, inflammation, and fibrosis in the ischemic kidney. These observations underscore the involvement of oxidative stress in renal injury in RAS and support a role for antioxidant vitamins in preserving the ischemic kidney.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalHypertension
Volume42
Issue number4 I
DOIs
StatePublished - Oct 1 2003

Keywords

  • Hypertension, renovascular
  • Kidney
  • Oxidative stress
  • Regional blood flow

ASJC Scopus subject areas

  • Internal Medicine

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