Article date: April 2006
By: Maria Rosaria Romano, Marcello D Lograno in Volume 147, Issue 8, pages 917-925
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 μM). Endothelium removal reduces cannabinoid agonist potency and efficacy.
The selective cannabinoid 1 (CB1) receptor antagonists SR141716A (100 nM) and AM251 (100 nM) 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, NG‐monomethyl‐L‐arginine (L‐NMMA, 300 μM), completely blocked the anandamide‐ and WIN55212‐2‐relaxant responses; by contrast, the nitric oxide donor S‐nitroso‐N‐acetylpenicillamine (SNAP, 100 μM) induced an increase in vasorelaxant responses to cannabinoid agonists.
Relaxations to anandamide and WIN55212‐2 were inhibited by iberiotoxin (IbTX, 200 nM), a blocker of large conductance, Ca2+‐activated K+ channel (BKCa), and by 4‐aminopyridine (4‐AP; 1 mM), a blocker of delayed rectifier K+ channel, whereas the blockade of KATP channels by glibenclamide (5 μM) and of small conductance Ca2+‐activated K+ channels (SKCa) by apamin (100 nM) did not produce any effects.
These data suggest that anandamide and WIN55212‐2 relax the bovine ophthalmic artery by involving CB1 the cannabinoid receptor‐sensitive pathway. In endothelium‐intact arteries, relaxation occurs through activation of nitric oxide synthase cyclic GMP and Ca2+‐activated K+ channels. They also cause endothelium‐independent relaxation by involving potassium channel opening.
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 μM). Endothelium removal reduces cannabinoid agonist potency and efficacy.
The selective cannabinoid 1 (CB1) receptor antagonists SR141716A (100 nM) and AM251 (100 nM) 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, NG‐monomethyl‐L‐arginine (L‐NMMA, 300 μM), completely blocked the anandamide‐ and WIN55212‐2‐relaxant responses; by contrast, the nitric oxide donor S‐nitroso‐N‐acetylpenicillamine (SNAP, 100 μM) induced an increase in vasorelaxant responses to cannabinoid agonists.
Relaxations to anandamide and WIN55212‐2 were inhibited by iberiotoxin (IbTX, 200 nM), a blocker of large conductance, Ca2+‐activated K+ channel (BKCa), and by 4‐aminopyridine (4‐AP; 1 mM), a blocker of delayed rectifier K+ channel, whereas the blockade of KATP channels by glibenclamide (5 μM) and of small conductance Ca2+‐activated K+ channels (SKCa) by apamin (100 nM) did not produce any effects.
These data suggest that anandamide and WIN55212‐2 relax the bovine ophthalmic artery by involving CB1 the cannabinoid receptor‐sensitive pathway. In endothelium‐intact arteries, relaxation occurs through activation of nitric oxide synthase cyclic GMP and Ca2+‐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
DOI: 10.1038/sj.bjp.0706687
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