Impaired vasorelaxation in inbred mice is associated with alterations in both nitric oxide and super oxide pathways

Chun Chen, Vyacheslav A. Korshunov, Michael P. Massett, Chen Yan, Bradford C. Berk

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways. Vasorelaxation to acetylcholine was significantly impaired in aortic rings from SJL compared to C3H or FVB mice (up to 40%). Relaxation to the endothelium-independent vasodilator sodium nitroprusside (SNP) in SJL mice was also significantly impaired at low concentrations, with decreases in sensitivity and maximal relaxation to SNP compared to C3H and FVB mice. Western blot analyses showed significantly decreased expression (∼40%) of eNOS, PKG and SOD-2 proteins in SJL vasculature compared to C3H. Intact aortas from SJL showed significantly increased nitrotyrosine and decreased SOD-2 expression compared to C3H by immunohistochemistry. Basal levels of superoxide in aortas from SJL were not significantly different than C3H as measured by dihydroethidine. In summary, relatively small alterations in redox (SOD-2) and NO pathways (eNOS and PKG) may contribute to significantly impaired vasorelaxation in SJL mice.

Original languageEnglish
Pages (from-to)504-512
Number of pages9
JournalJournal of Vascular Research
Volume44
Issue number6
DOIs
StatePublished - Oct 2007

Keywords

  • Endothelium
  • Inbred mice
  • Nitric oxide
  • SJL
  • SOD-2
  • Vascular reactivity

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