Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.

Azza B. El-Remessy, Huda E. Tawfik, Suraporn Matragoon, Bindu Pillai, Ruth B. Caldwell, R. William Caldwell

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.

Original languageEnglish (US)
Pages (from-to)247861
Number of pages1
JournalExperimental diabetes research
Volume2010
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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