Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide

Rommel C. Morales, Edward S M Bahnson, George E. Havelka, Nadiezhda Cantu-Medellin, Eric E. Kelley, Melina R. Kibbe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Background: Nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia following arterial injury in male versus female rodents, though the etiology is unclear. Given that superoxide (O2•-) regulates cellular proliferation, and NO regulates superoxide dismutase-1 (SOD-1) in the vasculature, we hypothesized that NO differentially regulates SOD-1 based on sex. Materials and methods: Male and female vascular smooth muscle cells (VSMC) were harvested from the aortae of Sprague-Dawley rats. O2•- levels were quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were detected by Western blot. SOD-1 activity was measured via colorimetric assay. The rat carotid artery injury model was performed on Sprague-Dawley rats ±NO treatment and SOD-1 protein levels were examined by Western blot. Results: In vitro, male VSMC have higher O2•- levels and lower SOD-1 activity at baseline compared to female VSMC (P<0.05). NO decreased O2•- levels and increased SOD-1 activity in male (P<0.05) but not female VSMC. NO also increased sod-1 gene expression and SOD-1 protein levels in male (P<0.05) but not female VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but NO increased SOD-1 levels 3-fold above controls in males, but returned to baseline in females. Conclusions: Our results provide evidence that regulation of the redox environment at baseline and following exposure to NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents.

Original languageEnglish (US)
Pages (from-to)226-233
Number of pages8
JournalRedox Biology
StatePublished - Apr 1 2015


  • Neointimal hyperplasia
  • Nitric oxide
  • Sex differences
  • Superoxide
  • Vascular

ASJC Scopus subject areas

  • Organic Chemistry


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