Potassium- and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase

Research output: Contribution to journalArticle

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Abstract

1. The contribution of an endothelium-derived hyperpolarizing factor (EDHF) was investigated in saphenous and mesenteric arteries from endothelial nitric oxide synthase (eNOS) (-/-) and (+/+) mice. 2. Acetylcholine-induced endothelium-dependent relaxation of saphenous arteries of eNOS(-/-) was resistant to N(ω)-nitro-L-arginine (L-NNA) and indomethacin, as well as the guanylyl cyclase inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a) quinoxalin-1-one(ODQ). 3. Potassium (K +) induced a dose-dependent vasorelaxation which was endothelium-independent and unaffected by either L-NNA or indomethacin in both saphenous and mesenteric arteries from eNOs(-/-) or (+/+) mice. 4. Thirty μM barium (Ba 2+) and 10 μM ouabain partially blocked potassium-induced, but had no effect on acetylcholine-induced vasorelaxation in saphenous arteries. 5. Acetylcholine-induced relaxation was blocked by a combination of charybdotoxin (ChTX) and apamin which had no effect on K +-induced relaxation, however, iberiotoxin (IbTX) was ineffective against either acetylcholine- or K +-induced relaxation. 6. Thirty μM Ba 2+ partially blocked both K +- and acetylcholine-induced relaxation of mesenteric arteries, and K +, but not acetylcholine-induced relaxation was totally blocked by the combination of Ba 2+ and ouabain. 7. These data indicate that acetylcholine-induced relaxation cannot be mimicked by elevating extracellular K + in saphenous arteries from either eNOS(-/-) or (+/+) mice, but K + may contribute to EDHF-mediated relaxation of mesenteric arteries.

Original languageEnglish
Pages (from-to)1194-1200
Number of pages7
JournalBritish Journal of Pharmacology
Volume129
Issue number6
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Vasodilation
Acetylcholine
Potassium
Mesenteric Arteries
Endothelium
Arteries
Ouabain
Indomethacin
Charybdotoxin
Apamin
Guanylate Cyclase
Barium
Arginine

Keywords

  • Endothelium-derived hyperpolarizing factor
  • ENOS knockout mice
  • Inward rectifier potassium channel (K(IR)) and Na /K ATPase
  • Saphenous and mesenteric arteries

ASJC Scopus subject areas

  • Pharmacology

Cite this

Potassium- and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase. / Ding, Hong; Kubes, Paul; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 129, No. 6, 2000, p. 1194-1200.

Research output: Contribution to journalArticle

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abstract = "1. The contribution of an endothelium-derived hyperpolarizing factor (EDHF) was investigated in saphenous and mesenteric arteries from endothelial nitric oxide synthase (eNOS) (-/-) and (+/+) mice. 2. Acetylcholine-induced endothelium-dependent relaxation of saphenous arteries of eNOS(-/-) was resistant to N(ω)-nitro-L-arginine (L-NNA) and indomethacin, as well as the guanylyl cyclase inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a) quinoxalin-1-one(ODQ). 3. Potassium (K +) induced a dose-dependent vasorelaxation which was endothelium-independent and unaffected by either L-NNA or indomethacin in both saphenous and mesenteric arteries from eNOs(-/-) or (+/+) mice. 4. Thirty μM barium (Ba 2+) and 10 μM ouabain partially blocked potassium-induced, but had no effect on acetylcholine-induced vasorelaxation in saphenous arteries. 5. Acetylcholine-induced relaxation was blocked by a combination of charybdotoxin (ChTX) and apamin which had no effect on K +-induced relaxation, however, iberiotoxin (IbTX) was ineffective against either acetylcholine- or K +-induced relaxation. 6. Thirty μM Ba 2+ partially blocked both K +- and acetylcholine-induced relaxation of mesenteric arteries, and K +, but not acetylcholine-induced relaxation was totally blocked by the combination of Ba 2+ and ouabain. 7. These data indicate that acetylcholine-induced relaxation cannot be mimicked by elevating extracellular K + in saphenous arteries from either eNOS(-/-) or (+/+) mice, but K + may contribute to EDHF-mediated relaxation of mesenteric arteries.",
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