Acetylcholine-induced relaxation of peripheral arteries isolated from mice lacking endothelial nitric oxide synthase

G. J. Waldron, Hong Ding, F. Lovren, P. Kubes, Christopher Triggle

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

1. Acetycholine-mediated relaxations in phenylephrine-contracted aortas, femoral and mesenteric resistance arteries were studied in vessels from endothelial nitric oxide synthase knock-out (eNOS -/-) and the corresponding wild-type strain (eNOS +/+) C57BL6/SV19 mice. 2. Aortas from eNOS (+/+) mice relaxed to acetylcholine in an endothelium-dependent N(G)-nitro-L-arginine (L-NOARG) sensitive manner. Aortas from eNOS (-/-) mice did not relax to acetylcholine but demonstrated enhanced sensitivity to both authentic NO and sodium nitroprusside. 3. Relaxation to acetylcholine in femoral arteries was partiaily inhibited by L-NOARG in vessels from eNOS (+/+) mice, but relaxation in eNOS (-/-) mice was insensitive to a combination of L-NOARG and indomethacin and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The L-NOARG/ODQ/indomethacin-insensitive relaxation to acetylcholine in femoral arteries was inhibited in the presence of elevated (30 mM) extracellular KCl. 4. In mesenteric resistance vessels from eNOS (+/+) mice, the acetylcholine-mediated relaxation response was completely inhibited by a combination of indomethacin and L-NOARG or by 30 mM KCl alone. In contrast, in mesenteric arteries from eNOS (-/-) mice, the acetylcholine-relaxation response was insensitive to a combination of L-NOARG and indomethacin, but was inhibited in the presence of 30 mM KCl. 5. These data indicate arteries from eNOS (-/-) mice demonstrate a supersensitivity to exogenous NO, and that acetylcholine-induced vasorelaxation of femoral and mesenteric vessels from eNOS (-/-) mice is mediated by an endothelium-derived factor that has properties of an EDHF but is neither NO nor prostacyclin. Furthermore, in mesenteric vessels, there is an upregulation of the role of EDHF in the absence of NO.

Original languageEnglish
Pages (from-to)653-658
Number of pages6
JournalBritish Journal of Pharmacology
Volume128
Issue number3
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Acetylcholine
Arteries
Nitroarginine
Indomethacin
Aorta
Mesenteric Arteries
Femoral Artery
Thigh
Endothelium
Guanylate Cyclase
Nitroprusside
Phenylephrine
Epoprostenol
Vasodilation
Arginine
Up-Regulation

Keywords

  • EDHF
  • Endothelium
  • eNOS knockout mice
  • NO
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology

Cite this

Acetylcholine-induced relaxation of peripheral arteries isolated from mice lacking endothelial nitric oxide synthase. / Waldron, G. J.; Ding, Hong; Lovren, F.; Kubes, P.; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 128, No. 3, 1999, p. 653-658.

Research output: Contribution to journalArticle

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AU - Ding, Hong

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AU - Triggle, Christopher

PY - 1999

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N2 - 1. Acetycholine-mediated relaxations in phenylephrine-contracted aortas, femoral and mesenteric resistance arteries were studied in vessels from endothelial nitric oxide synthase knock-out (eNOS -/-) and the corresponding wild-type strain (eNOS +/+) C57BL6/SV19 mice. 2. Aortas from eNOS (+/+) mice relaxed to acetylcholine in an endothelium-dependent N(G)-nitro-L-arginine (L-NOARG) sensitive manner. Aortas from eNOS (-/-) mice did not relax to acetylcholine but demonstrated enhanced sensitivity to both authentic NO and sodium nitroprusside. 3. Relaxation to acetylcholine in femoral arteries was partiaily inhibited by L-NOARG in vessels from eNOS (+/+) mice, but relaxation in eNOS (-/-) mice was insensitive to a combination of L-NOARG and indomethacin and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The L-NOARG/ODQ/indomethacin-insensitive relaxation to acetylcholine in femoral arteries was inhibited in the presence of elevated (30 mM) extracellular KCl. 4. In mesenteric resistance vessels from eNOS (+/+) mice, the acetylcholine-mediated relaxation response was completely inhibited by a combination of indomethacin and L-NOARG or by 30 mM KCl alone. In contrast, in mesenteric arteries from eNOS (-/-) mice, the acetylcholine-relaxation response was insensitive to a combination of L-NOARG and indomethacin, but was inhibited in the presence of 30 mM KCl. 5. These data indicate arteries from eNOS (-/-) mice demonstrate a supersensitivity to exogenous NO, and that acetylcholine-induced vasorelaxation of femoral and mesenteric vessels from eNOS (-/-) mice is mediated by an endothelium-derived factor that has properties of an EDHF but is neither NO nor prostacyclin. Furthermore, in mesenteric vessels, there is an upregulation of the role of EDHF in the absence of NO.

AB - 1. Acetycholine-mediated relaxations in phenylephrine-contracted aortas, femoral and mesenteric resistance arteries were studied in vessels from endothelial nitric oxide synthase knock-out (eNOS -/-) and the corresponding wild-type strain (eNOS +/+) C57BL6/SV19 mice. 2. Aortas from eNOS (+/+) mice relaxed to acetylcholine in an endothelium-dependent N(G)-nitro-L-arginine (L-NOARG) sensitive manner. Aortas from eNOS (-/-) mice did not relax to acetylcholine but demonstrated enhanced sensitivity to both authentic NO and sodium nitroprusside. 3. Relaxation to acetylcholine in femoral arteries was partiaily inhibited by L-NOARG in vessels from eNOS (+/+) mice, but relaxation in eNOS (-/-) mice was insensitive to a combination of L-NOARG and indomethacin and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The L-NOARG/ODQ/indomethacin-insensitive relaxation to acetylcholine in femoral arteries was inhibited in the presence of elevated (30 mM) extracellular KCl. 4. In mesenteric resistance vessels from eNOS (+/+) mice, the acetylcholine-mediated relaxation response was completely inhibited by a combination of indomethacin and L-NOARG or by 30 mM KCl alone. In contrast, in mesenteric arteries from eNOS (-/-) mice, the acetylcholine-relaxation response was insensitive to a combination of L-NOARG and indomethacin, but was inhibited in the presence of 30 mM KCl. 5. These data indicate arteries from eNOS (-/-) mice demonstrate a supersensitivity to exogenous NO, and that acetylcholine-induced vasorelaxation of femoral and mesenteric vessels from eNOS (-/-) mice is mediated by an endothelium-derived factor that has properties of an EDHF but is neither NO nor prostacyclin. Furthermore, in mesenteric vessels, there is an upregulation of the role of EDHF in the absence of NO.

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