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Involvement of CB 1 cannabinoid receptors in the EDHF‐dependent vasorelaxation in rabbits
Author(s) -
Niederhoffer Nathalie,
Szabo Bela
Publication year - 1999
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.0702452
Subject(s) - cannabinoid , vasodilation , cannabinoid receptor , chemistry , pharmacology , acetylcholine , agonist , endocrinology , cannabinoid receptor antagonist , medicine , receptor , biochemistry
It was recently suggested that an endogenous cannabinoid could represent an endothelium‐derived hyperpolarizing factor (EDHF). The aim of the present study was to clarify whether CB 1 cannabinoid receptors are involved in the nitric oxide (NO)‐ and prostanoid‐independent vasodilation produced by acetylcholine in rabbits. Pithed rabbits received indomethacin. Noradrenaline was infused to raise blood pressure, and vasodilation was elicited by bolus injections of acetylcholine. The NO‐synthase inhibitor N ω ‐nitro‐ L ‐arginine methylester inhibited the acetylcholine‐evoked vasodilation by about 40%. The remaining vasodilation was unaffected by the CB 1 cannabinoid receptor antagonist SR141716A, but was inhibited by the potassium channel blocker tetraethylammonium. In addition, the mixed CB 1 /CB 2 cannabinoid receptor agonist WIN55212‐2 did not elicit vasodilation. No CB 1 cannabinoid receptors were involved in the prostanoid‐ and NO‐independent vasodilation produced by acetylcholine. An exogenous cannabinoid also did not cause vasodilation. Therefore, it is unlikely that an endogenous cannabinoid serves as an EDHF acting at smooth muscle CB 1 cannabinoid receptors in the rabbit.British Journal of Pharmacology (1999) 126 , 1383–1386; doi: 10.1038/sj.bjp.0702452