Reactive oxygen species cause endothelial dysfunction in chronic flow overload

X. Lu, X. Guo, C. D. Wassall, M. D. Kemple, J. L. Unthank, G. S. Kassab

Research output: Contribution to journalArticle

19 Scopus citations


Although elevation of shear stress increases production of vascular reactive oxygen species (ROS), the role of ROS in chronic flow overload (CFO) has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. In six swine, CFO in carotid arteries was induced by contralateral ligation for 1 wk. In an additional group, six swine received apocynin (NADPH oxidase blocker and anti-oxidant) treatment in conjunction with CFO for 1 wk. The blood flow in carotid arteries increased from 189.2 ± 25.3 ml/min (control) to 369.6 ± 61.9 ml/min (CFO), and the arterial diameter increased by 8.6%. The expressions of endothelial nitric oxide synthase (eNOS), p22/p47phox, and NOX2/NOX4 were upregulated. ROS production increased threefold in response to CFO. The endothelium-dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. Although the process of CFO remodeling to restore the wall shear stress has been thought of as a physiological response, the present data implicate NADPH oxidase-produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO.

Original languageEnglish (US)
Pages (from-to)520-527
Number of pages8
JournalJournal of Applied Physiology
Issue number2
StatePublished - Feb 2011


  • Chronic flow overload
  • Endothelial dysfunction
  • NADPH oxidase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Reactive oxygen species cause endothelial dysfunction in chronic flow overload'. Together they form a unique fingerprint.

  • Cite this

    Lu, X., Guo, X., Wassall, C. D., Kemple, M. D., Unthank, J. L., & Kassab, G. S. (2011). Reactive oxygen species cause endothelial dysfunction in chronic flow overload. Journal of Applied Physiology, 110(2), 520-527.