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Anandamide‐induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels
Author(s) -
Grainger J,
BoachieAnsah G
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704340
Subject(s) - anandamide , chemistry , capsazepine , endocannabinoid system , cannabinoid receptor , iberiotoxin , medicine , apamin , endocrinology , potassium channel , cannabinoid , potassium channel blocker , pharmacology , agonist , trpv1 , biochemistry , receptor , transient receptor potential channel
The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro . In endothelium‐intact rings precontracted to the thromboxane A 2 mimetic, U46619, anandamide (0.01 – 30 μ M ) induced slowly developing concentration‐dependent relaxations (p EC 50 [negative log of EC 50 ]=6.1±0.1; R max [maximum response]=81±4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration‐relaxation curve without modifying R max . Methanandamide was without effect on U46619‐induced tone. The anandamide‐induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 μ M ), the vanilloid receptor antagonist, capsazepine (3 and 10 μ M ) or the nitric oxide synthase inhibitor, L ‐NAME (100 μ M ). The cyclo‐oxygenase inhibitor, indomethacin (3 and 10 μ M ) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 μ M ), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 μ M ), shifted the anandamide concentration‐response curve to the right. Precontraction of endothelium‐intact rings with 25 m M KCl attenuated the anandamide‐induced relaxations (R max =7±7%), as did K + channel blockade with tetraethylammonium (TEA; 3 μ M ) or iberiotoxin (100 n M ). Blockade of small conductance, Ca 2+ ‐activated K + channels, delayed rectifier K + channels, K ATP channels or inward rectifier K + channels was without effect. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels.British Journal of Pharmacology (2001) 134 , 1003–1012; doi: 10.1038/sj.bjp.0704340