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

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Abstract

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number6 49-6
StatePublished - 2001

Fingerprint

Nitric Oxide Synthase Type III
Arterioles
Knockout Mice
Dilatation
Skeletal Muscle
Miconazole
Indomethacin
Nitric Oxide
Calcium-Activated Potassium Channels
endothelium-dependent hyperpolarization factor
Vasodilation
Cytochrome P-450 Enzyme System
Prostaglandins
Endothelium
Smooth Muscle
Acids

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Huang, A., Sun, D., Carroll, M. A., Jiang, H., Smith, C. J., Connetta, J. 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).

EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. / Huang, An; Sun, Dong; Carroll, Mairead A.; Jiang, Houli; Smith, Carolyn J.; Connetta, Joseph A.; Falck, J R; Shesely, Edward G.; Koller, Akos; Kaley, Gabor.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 6 49-6, 2001.

Research output: Contribution to journalArticle

Huang, A, Sun, D, Carroll, MA, Jiang, H, Smith, CJ, Connetta, JA, Falck, JR, Shesely, EG, 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, vol. 280, no. 6 49-6.
Huang, An ; Sun, Dong ; Carroll, Mairead A. ; Jiang, Houli ; Smith, Carolyn J. ; Connetta, Joseph A. ; Falck, J R ; Shesely, Edward G. ; Koller, Akos ; Kaley, Gabor. / EDHF mediates flow-induced dilation in skeletal muscle arterioles of female eNOS-KO mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2001 ; Vol. 280, No. 6 49-6.
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abstract = "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.",
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AU - Carroll, Mairead A.

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AU - Smith, Carolyn J.

AU - Connetta, Joseph A.

AU - Falck, J R

AU - Shesely, Edward G.

AU - Koller, Akos

AU - Kaley, Gabor

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N2 - 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.

AB - 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.

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