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Cannabinoid agonists induce relaxation in the bovine ophthalmic artery: evidences for CB 1 receptors, nitric oxide and potassium channels
Author(s) -
Romano Maria Rosaria,
Lograno Marcello D
Publication year - 2006
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.0706687
Subject(s) - apamin , chemistry , anandamide , cannabinoid , iberiotoxin , pharmacology , cannabinoid receptor , agonist , am251 , nitric oxide , potassium channel , glibenclamide , biophysics , medicine , endocrinology , receptor , biochemistry , biology , organic chemistry , diabetes mellitus
Glaucoma pathophysiology appears to involve vascular deficits, which may contribute to initiation and progression of the disease. Anandamide, the endogenous cannabinoid ligand, and WIN55212‐2, a synthetic cannabinoid agonist, are able to evoke concentration‐dependent relaxations in bovine ophthalmic artery rings, precontracted with 5‐hydroxytryptamine (5‐HT) (1 μ M ). Endothelium removal reduces cannabinoid agonist potency and efficacy. The selective cannabinoid 1 (CB 1 ) receptor antagonists SR141716A (100 n M ) and AM251 (100 n M ) cause a shift to the right in the concentration–response curves to anandamide and WIN55212‐2 in arterial rings both in the presence and in the absence of endothelium. In endothelium‐intact arteries, the nitric oxide synthase inhibitor, N G ‐monomethyl‐ L ‐arginine ( L ‐NMMA, 300 μ M ), completely blocked the anandamide‐ and WIN55212‐2‐relaxant responses; by contrast, the nitric oxide donor S ‐nitroso‐ N ‐acetylpenicillamine (SNAP, 100 μ M ) induced an increase in vasorelaxant responses to cannabinoid agonists. Relaxations to anandamide and WIN55212‐2 were inhibited by iberiotoxin (IbTX, 200 n M ), a blocker of large conductance, Ca 2+ ‐activated K + channel (BK Ca ), and by 4‐aminopyridine (4‐AP; 1 m M ), a blocker of delayed rectifier K + channel, whereas the blockade of K ATP channels by glibenclamide (5 μ M ) and of small conductance Ca 2+ ‐activated K + channels (SK Ca ) by apamin (100 n M ) did not produce any effects. These data suggest that anandamide and WIN55212‐2 relax the bovine ophthalmic artery by involving CB 1 the cannabinoid receptor‐sensitive pathway. In endothelium‐intact arteries, relaxation occurs through activation of nitric oxide synthase cyclic GMP and Ca 2+ ‐activated K + channels. They also cause endothelium‐independent relaxation by involving potassium channel opening.British Journal of Pharmacology (2006) 147 , 917–925. doi: 10.1038/sj.bjp.0706687