Exacerbation of endothelial dysfunction during the progression of diabetes: Role of oxidative stress

An Huang, Yang Ming Yang, Attila Feher, Zsolt Bagi, Gabor Kaley, Dong Sun

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

To test the deterioration of endothelial function during the progression of diabetes, shear stressinduced dilation (SSID; 10, 20, and 40 dyn/cm 2) was determined in isolated mesenteric arteries (80-120 μm in diameter) of 6-wk (6W), 3-mo (3M), and 9-mo (9M)-old male db/db mice and their wild-type (WT) controls. Nitric oxide (NO)-mediated SSID was comparable in 6W WT and db/db mice, but the dilation was significantly reduced in 3M db/db mice and declined further in 9M db/db mice. Vascular superoxide production was progressively increased in 3M and 9M db/db mice, associated with an increased expression of NADPH oxidase. Inhibition of NADPH oxidase significantly improved NOmediated SSID in arteries of 3M, but not in 9M, db/db mice. Although endothelial nitric oxide synthase (eNOS) expression was comparable in all groups, a progressive reduction in shear stress-induced eNOS phosphorylation existed in vessels of 3M and 9M db/db mice. Moreover, inducible NOS (iNOS) that was not detected in WT, nor in 6W and 3M db/db mice, was expressed in vessels of 9M db/db mice. A significantly increased expression of nitrotyrosine in total protein and immunoprecipitated eNOS was also found in vessels of 9M db/db mice. Thus, impaired NO bioavailability plays an essential role in the endothelial dysfunction of diabetic mice, which becomes aggravated when endothelial nitrosative stress is further activated via perhaps, an additional iNOS-mediated pathway during the progression of diabetes.

Original languageEnglish (US)
Pages (from-to)674-681
Number of pages8
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume302
Issue number6
DOIs
Publication statusPublished - Mar 1 2012
Externally publishedYes

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Keywords

  • Diabetes
  • Endothelium
  • Nitric oxide
  • Nitrotyrosine
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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