Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in guinea-pig cerebral and mesenteric resistance vessels

H. Dong, Y. Jiang, W. C. Cole, Christopher Triggle

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

1. In the presence of L-NNA (100 μM), indomethacin (10 μM) and ODQ (10 μM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K +, indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). 2. In cerebral arteries, charybdotoxin (ChTX; 0.1 μM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 μM), 4-aminopyridine (4-AP, 1 mM), or barium (30 μM) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 μM) had no affect in either the mesenteric or cerebral artery. 3. Neither clotrimazole (1 μM) nor 7-ethoxyresorufin (3 μM) affected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 μM), a selective anandamide transport inhibitor, did not affect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 μM) almost abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K + (5-20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. 4. These data suggest that in the guinea-pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K +.

Original languageEnglish
Pages (from-to)1983-1991
Number of pages9
JournalBritish Journal of Pharmacology
Volume130
Issue number8
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Mesenteric Arteries
Cerebral Arteries
Vasodilation
Endothelium
Guinea Pigs
Pharmacology
Charybdotoxin
Acetylcholine
Indomethacin
Clotrimazole
Apamin
4-Aminopyridine
Glyburide
Transcription Factor AP-1
Middle Cerebral Artery
Ouabain
Barium
Vasoconstriction
Histamine
iberiotoxin

Keywords

  • Acetylcholine
  • Calcium-activated potassium channels
  • Cytochrome P450
  • Delayed rectifier potassium channels
  • Endothelium-derived hyperpolarizing factor (EDHF)
  • Inwardly rectifying potassium channels
  • Mesenteric artery
  • Middle cerebral artery

ASJC Scopus subject areas

  • Pharmacology

Cite this

Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in guinea-pig cerebral and mesenteric resistance vessels. / Dong, H.; Jiang, Y.; Cole, W. C.; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 130, No. 8, 2000, p. 1983-1991.

Research output: Contribution to journalArticle

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N2 - 1. In the presence of L-NNA (100 μM), indomethacin (10 μM) and ODQ (10 μM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K +, indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). 2. In cerebral arteries, charybdotoxin (ChTX; 0.1 μM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 μM), 4-aminopyridine (4-AP, 1 mM), or barium (30 μM) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 μM) had no affect in either the mesenteric or cerebral artery. 3. Neither clotrimazole (1 μM) nor 7-ethoxyresorufin (3 μM) affected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 μM), a selective anandamide transport inhibitor, did not affect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 μM) almost abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K + (5-20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. 4. These data suggest that in the guinea-pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K +.

AB - 1. In the presence of L-NNA (100 μM), indomethacin (10 μM) and ODQ (10 μM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K +, indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). 2. In cerebral arteries, charybdotoxin (ChTX; 0.1 μM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 μM), 4-aminopyridine (4-AP, 1 mM), or barium (30 μM) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 μM) had no affect in either the mesenteric or cerebral artery. 3. Neither clotrimazole (1 μM) nor 7-ethoxyresorufin (3 μM) affected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 μM), a selective anandamide transport inhibitor, did not affect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 μM) almost abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K + (5-20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. 4. These data suggest that in the guinea-pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K +.

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KW - Inwardly rectifying potassium channels

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KW - Middle cerebral artery

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