Peroxynitrite Mediates Diabetes-Induced Endothelial Dysfunction: Possible Role of Rho Kinase Activation
AuthorsEl-Remessy, Azza B.
Tawfik, Huda E.
Caldwell, Ruth B.
Caldwell, Robert William
MetadataShow full item record
AbstractEndothelial 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, 15â 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.
CitationExp Diabetes Res. 2010 Nov 1; 2010:247861
- Alpha-linolenic acid intake prevents endothelial dysfunction in high-fat diet-fed streptozotocin rats and underlying mechanisms.
- Authors: Zhang W, Fu F, Tie R, Liang X, Tian F, Xing W, Li J, Ji L, Xing J, Sun X, Zhang H
- Issue date: 2013 Nov
- RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels.
- Authors: Sun Z, Wu X, Li W, Peng H, Shen X, Ma L, Liu H, Li H
- Issue date: 2016 Oct 11
- Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats.
- Authors: Obrosova IG, Drel VR, Oltman CL, Mashtalir N, Tibrewala J, Groves JT, Yorek MA
- Issue date: 2007 Dec
- Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity.
- Authors: Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, Lopez BL, Tao L, Goldstein BJ, Gao F, Ma XL
- Issue date: 2007 Dec
- Role of oxidative stress in multiparity-induced endothelial dysfunction.
- Authors: Tawfik HE, Cena J, Schulz R, Kaufman S
- Issue date: 2008 Oct