Cannabinoid agonists induce relaxation in the bovine ophthalmic artery: evidences for CB₁ receptors, nitric oxide and potassium channels

Abstract

1 Glaucoma pathophysiology appears to involve vascular deficits, which may contribute to initiation and progression of the disease. 2 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 mM). Endothelium removal reduces cannabinoid agonist potency and efficacy. 3 The selective cannabinoid 1 (CB 1 ) 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. 4 In endothelium-intact arteries, the nitric oxide synthase inhibitor, N G -monomethyl-L-arginine (L-NMMA, 300 mM), completely blocked the anandamide-and WIN55212-2-relaxant responses; by contrast, the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP, 100 mM) induced an increase in vasorelaxant responses to cannabinoid agonists. 5 Relaxations to anandamide and WIN55212-2 were inhibited by iberiotoxin (IbTX, 200 nM), a blocker of large conductance, Ca 2 þ -activated K þ channel (BK Ca ), and by 4-aminopyridine (4-AP; 1 mM), a blocker of delayed rectifier K þ channel, whereas the blockade of K ATP channels by glibenclamide (5 mM) and of small conductance Ca 2 þ -activated K þ channels (SK Ca ) by apamin (100 nM) did not produce any effects. 6 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 þ -activated K þ channels. They also cause endothelium-independent relaxation by involving potassium channel opening.

Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users

“…In animal studies, there is a large evidence supporting a role for ECS in improving endothelial function and nitric oxide production 37 as well as THC has been shown to Endothelial dysfunction in erectile dysfunction A Aversa et al improve endothelium-dependent relaxation. [38][39][40] In addition, the EC anandamide, improves neurogenic relaxation of corpus cavernosum in diabetic rats.…”

Aplicaciones de los cannabinoides en glaucoma

“…El marcaje resultó moderado-ligero en el esfín-ter pupilar. También es interesante la detección de receptores de cannabinoides funcionales a nivel de las arterias oftálmicas bovinas 28 .…”

“…se demostraron receptores CB1 en fibras musculares lisas y endoteliales aórticas 59 y posteriormente a nivel de arterias bovinas oftálmicas 28 .…”

“…Los agonistas de cannabinoides producen un efecto relajante vascular a través de la activación de canales de K+, por la vía GMP-c y del óxido nítrico 28 . La AEA y el WIN 55212-2 producen un efecto vasodilatador dosis-dependiente a través de factores relajantes derivados del endotelio como el óxido nítrico 62 , por estimulación de receptores CB1 y de vaniloides 28 .…”

“…La AEA y el WIN 55212-2 producen un efecto vasodilatador dosis-dependiente a través de factores relajantes derivados del endotelio como el óxido nítrico 62 , por estimulación de receptores CB1 y de vaniloides 28 .…”