Adenosine enhances the relaxing influence of rat and bovine retinal tissue

Retinal tissue from different species continuously releases a factor lowering tone of isolated arteries. This was demonstrated by placing retinal tissue in close proximity to an isolated artery. This factor is called the "retinal relaxing factor" (RRF) (Delaey & Van de Voorde, Circ Res 1998, 83:714-720). The potential influence of adenosine on this relaxing influence was investigated using isometric tension recording of isolated arteries. The presence of bovine retinal tissue enhanced the vasorelaxing effect of adenosine on isolated bovine retinal artery. The presence of a non-selective adenosine receptor antagonist (8-(p-sulfophenyl)theophylline, 0.1 mM) showed a significant blocking effect of adenosine. When the retinal arteries were contracted with 120 mM K+, adenosine no longer induced relaxation of the preparation with bovine retinal tissue. This is in line with the concept that adenosine enhances the influence of RRF. Neither a NO-synthase inhibitor (nitro-L-arginine, 0.1 mM), a cyclooxygenase inhibitor (indomethacin, 10 mM) or an epoxyeicosatrienoic acid inhibitor (miconazole, 10 mM) influenced the enhanced vasodilating effect of adenosine on retinal arteries in the presence of bovine retinal tissue. In rat carotid artery adenosine elicited no relaxation in the absence of rat or porcine retinal tissue. However, a small relaxation is observed in the presence of rat retinal tissue, but not in the presence of porcine retina. In conclusion, our findings indicate that adenosine potentiates the relaxing influence of bovine retinal tissue on bovine retinal artery. Neither NO, cyclooxygenase metabolites of epoxyeicosatrienoic acids seem to be involved in this enhanced vasorelaxing response. Our results suggest the involvement of RRF released from bovine retina. The fact that rat retinal tissue, but not porcine retinal tissue, enhances the relaxing effect of adenosine on rat carotid artery, indicates species differences

Clozapine directly relaxes bovine retinal arteries

Purpose: It was suggested that clozapine might be helpful in the development of new antiglaucoma agents, as it combines lowering the intraocular pressure after topical instillation with vasodilation. This study aimed to evaluate and characterize the vasodilatory effect of clozapine in isolated bovine retinal arteries ( BRAs). Methods: Retinal arteries were isolated from bovine eyes and mounted in the organ bath of a small vessel myograph. Results: Cumulative addition of clozapine ( 1 nM to 10 mu M) caused a concentration- dependent relaxation of the BRAs. Removal of the endothelium, inhibition of nitric oxide synthase and of soluble guanylyl cyclase reduced the clozapine response, whereas cyclooxygenase inhibition had no influence. A Ca2+ channel activator, a 5- hydroxytryptamine receptor antagonist, and an adenosine receptor antagonist failed in affecting the clozapine- induced relaxations. Conclusions: Clozapine relaxes bovine retinal arteries. Endothelium- derived NO seems to be involved, whereas prostanoids, calcium entry blockade, 5- HT7 receptor stimulation, and adenosine receptor stimulation do not