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

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 endotheliu...

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Bibliographic Details
Published in:British journal of pharmacology 2000-08, Vol.130 (8), p.1983-1991
Main Authors: Dong, Hui, Jiang, Yanfen, Cole, William C, Triggle, Christopher R
Format: Article
Language:English
Subjects:
4-Aminopyridine - pharmacology
Acetylcholine
Acetylcholine - pharmacology
Anandamide
Animals
Arachidonic Acids - pharmacology
Barium
Biological and medical sciences
Biological Factors - physiology
calcium‐activated potassium channels
Cell physiology
Cerebral Arteries - drug effects
Cerebral Arteries - physiology
Charybdotoxin
Charybdotoxin - pharmacology
Clotrimazole
Cytochrome P-450 Enzyme System - metabolism
cytochrome P450
Data processing
delayed rectifier potassium channels
Dose-Response Relationship, Drug
Endothelium, Vascular - physiology
endothelium‐derived hyperpolarizing factor (EDHF)
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
glibenclamide
Glyburide - pharmacology
Guinea Pigs
Histamine
Imidazoles - pharmacology
In Vitro Techniques
Indomethacin
Indomethacin - pharmacology
inwardly rectifying potassium channels
Male
Mesenteric Arteries - drug effects
Mesenteric Arteries - physiology
mesenteric artery
middle cerebral artery
Molecular and cellular biology
Muscle contraction
Nitric Oxide - physiology
Nitroarginine - pharmacology
Ouabain
Ouabain - pharmacology
Oxadiazoles - pharmacology
Pharmacology
Potassium
Potassium Channel Blockers
Potassium Channels - physiology
Quinoxalines - pharmacology
Vasodilation
Vasodilation - drug effects
Vasodilator Agents - pharmacology
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Summary: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). 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. 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. 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+. British Journal of Pharmacology (2000) 130, 1983–1991; doi:10.1038/sj.bjp.0703474
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0703474