EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice

An Huang, Dong Sun, Mairead A. Carroll, Houli Jiang, Carolyn J. Smith, Joseph A. Connetta, J R Falck, Edward G. Shesely, Akos Koller, Gabor Kaley

Research output: Contribution to journalArticle

111 Scopus citations


Vasodilation to increases in flow was studied in isolated gracilis muscle arterioles of female endothelial nitric oxide synthase (eNOS)-knockout (KO) and female wild-type (WT) mice. Dilation to flow (0-10 μl/min) was similar in the two groups, yet calculated wall shear stress was significantly greater in arterioles of eNOS-KO than in arterioles of WT mice. Indomethacin, which inhibited flow-induced dilation in vessels of WT mice by ∼40%, did not affect the responses of eNOS-KO mice, whereas miconazole and 6-(2-proparglyoxyphenyl)hexanoic acid (PPOH) abolished the responses. Basal release of epoxyeicosatrienonic acids from arterioles was inhibited by PPOH. Iberiotoxin eliminated flow-induced dilation in arterioles of eNOS-KO mice but had no effect on arterioles of WT mice. In WT mice, neither Nω-nitro-L-arginine methyl ester nor miconazole alone affected flow-induced dilation. Combination of both inhibitors inhibited the responses by ∼50%. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) alone inhibited flow-induced dilation by ∼49%. ODQ + indomethacin eliminated the responses. Thus, in arterioles of female WT mice, nitric oxide and prostaglandins mediate flow-induced dilation. When eNOS is inhibited, endothelium-derived hyperpolarizing factor substitutes for nitric oxide. In female eNOS-KO mice, metabolites of cytochrome P-450, via activation of large-conductance Ca2+-activated K+ channels of smooth muscle, mediate entirely the arteriolar dilation to flow.

Original languageEnglish (US)
Pages (from-to)H2462-H2469
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 49-6
StatePublished - Jul 3 2001


  • Cytochrome P-450 metabolites
  • Hyperpolarizing factor
  • Nitric oxide
  • Potassium channels
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Huang, A., Sun, D., Carroll, M. A., Jiang, H., Smith, C. J., Connetta, J. A., Falck, J. R., Shesely, E. G., Koller, A., & Kaley, G. (2001). EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. American Journal of Physiology - Heart and Circulatory Physiology, 280(6 49-6), H2462-H2469.