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Mechanisms of anandamide‐induced vasorelaxation in rat isolated coronary arteries
Author(s) -
White Richard,
Vanessa Ho W S,
Bottrill Fiona E,
Ford William R,
Hiley C Robin
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.0704333
Subject(s) - anandamide , capsazepine , chemistry , endocannabinoid system , palmitoylethanolamide , cannabinoid , cannabinoid receptor , pharmacology , apamin , agonist , medicine , endocrinology , trpv1 , receptor , potassium channel , biochemistry , transient receptor potential channel
The cannabinoid arachidonyl ethanolamide (anandamide) caused concentration‐dependent relaxation of 5‐HT‐precontracted, myograph‐mounted, segments of rat left anterior descending coronary artery. This relaxation was endothelium‐independent, unaffected by the fatty acid amide hydrolase inhibitor, arachidonyl trifluoromethyl ketone (10 μ M ), and mimicked by the non‐hydrolysable anandamide derivative, methanandamide. Relaxations to anandamide were attenuated by the cannabinoid receptor antagonist, SR 141716A (3 μ M ), but unaffected by AM 251 (1 μ M ) and AM 630 (1 μ M ), more selective antagonists of cannabinoid CB 1 and CB 2 receptors respectively. Palmitoylethanolamide, a selective CB 2 receptor agonist, did not relax precontracted coronary arteries. Anandamide relaxations were not affected by inhibition of sensory nerve transmission with capsaicin (10 μ M ) or blockade of vanilloid VR1 receptors with capsazepine (5 μ M ). Nevertheless capsaicin relaxed coronary arteries in a concentration‐dependent and capsazepine‐sensitive manner, confirming functional sensory nerves were present. In contrast, capsazepine and capsaicin did inhibit anandamide relaxations in methoxamine‐precontracted rat small mesenteric arteries. Relaxations to anandamide were inhibited by TEA (1 m M ) or iberiotoxin (50 n M ), blockers of large conductance, Ca 2+ ‐activated K + channels (BK Ca ). Gap junction inhibition with 18α‐glycyrrhetinic acid (100 μ M ) did not affect anandamide relaxations. This study shows anandamide relaxes the rat coronary artery by a novel mechanism. Anandamide‐induced relaxations do not involve the endothelium, degradation into active metabolites, or activation of cannabinoid CB 1 or CB 2 receptors, but may involve activation of BK Ca . Vanilloid receptor activation also has no role in the effects of anandamide in coronary arteries, even though functional sensory nerves are present.British Journal of Pharmacology (2001) 134 , 921–929; doi: 10.1038/sj.bjp.0704333