Retina evokes biphasic relaxations in retinal artery unrelated to endothelium, K-V, K-ATP, K-Ca channels and methyl palmitate

Retinal relaxing factor (RRF) is suggested to be released from the retina and to contribute in the maintenance of retinal arterial tone. Herein, we aimed to clarify the effects of retinal tissue in isolated bovine retinal arteries in comparison with choroidal tissue and to evaluate the possible role of endothelium and potassium channels. In parallel, the effects of palmitic acid methyl ester (FAME), a putative vasodilator proposed to be released from the retina, was also examined. A piece of bovine retinal or choroidal tissue was placed within a close proximity on top of retinal arteries mounted in a wire myograph and precontracted with noradrenaline, prostaglandin F-2 alpha, endothelin-1, thromboxane A(2) mimetic, U46619 or potassium (K+). To elucidate possible mechanisms in the effects of retinal tissue, retinal arteries were either deendothelized or incubated with inhibitors of endothelial vasodilators, i.e. nitric oxide (NO) and prostaglandins, or K+ channels. Unlike the choroid, retinal tissue produced rapid, biphasic and complete relaxations in isolated bovine retinal arteries precontracted with various spasmogens acting on distinct receptors. Endothelium removal or preincubation of retinal arteries with inhibitors of NO synthase; L-NOARG (10(-4) M), guanylate cyclase; ODQ (10(-5) M) and cyclooxygenase; indomethacin (10(-5) M), did not cause a significant difference in the relaxation profile. Additionally, retinal relaxations remained unchanged in the presence of respective inhibitors of ATP-sensitive (K-ATP) (glibenclamide, 10(-5) M), voltage-dependent (K-V) (4-aminopyridine, 2 x 10(-3) M), and calcium-activated (K-Ca) (tetraethylammonium 10 mM; charybdotoxin, 10(-7) M; and apamin, 5 x 10(-7) M) K+ channels. Thus, our results provide novel evidence regarding the biphasic relaxing profile of RRF in the retinal artery which was unrelated to endothelium and K+ channels (K-ATP, K-V and K-Ca). Interestingly, PAME (10(-14)-10(-5) M) did not provoke a relaxation in bovine retinal artery suggesting no association with RRF. (C) 2011 Elsevier Inc. All rights reserved

NaHS induces relaxation response in prostaglandin F-2 alpha precontracted bovine retinal arteries partially via K-v and K-ir channels

Hydrogen sulphide (H2S) is known to be produced endogenously in ocular tissues with the highest levels in the retina and cornea. However, it is yet unclear whether it can modulate retinal arterial tone. Herein, we aimed to investigate the effectiveness and the mechanism of the action of H2S in the isolated bovine retinal arteries. For this purpose, the probable vasorelaxant and inhibitory effects of H2S on vascular reactivity were tested comparatively in the retinal arteries by using the donor, sodium hydrosulphide (NaHS). Thereafter, in relation to the mechanism of action of H2S, the role of nitric oxide (NO) and endothelial vasodilators of cyclooxygenase pathway as well as ATP-sensitive potassium channel (K-ATP), voltage-dependent potassium channel (K-v), calcium-activated potassium channel (K-Ca(++)), inwardly rectifying potassium channel (K-ir), L-type voltage-dependent calcium channel and adenylate cyclase pathway were evaluated. NaHS (1 mu M-3 mM) displayed prominent relaxations over the concentrations of 300 mu M in both PGF(2 alpha) and K+ precontracted retinal arteries. Comparatively, in the presence of NaHS (3 mM) pretreatment, the maximum contractile responses and pEC(50) values to PGF(2 alpha) and K+ were significantly reduced as well. Neither the presence of the known inhibitors of NO synthase, guanylate cyclase, cyclooxygenase, adenylate cyclase, KA(ATP) and K-Ca(++) type K+ channels, and L-type voltage-dependent calcium channels nor the removal of endothelium, modified the relaxation response to NaHS in retinal arteries. However, a remarkable decrease was observed in the presence of the inhibitors of K-v or K-ir type K+ channels. In addition, administration of L-cysteine (1 mu M-3 mM), the precursor of H2S, induced a modest relaxation response in PGF(2 alpha) precontracted retinal arteries, which was significantly decreased in the presence of cystathionine-beta-synthase (CBS) inhibitor, aminooxyacetic acid, but was unmodified in the presence of the cystathionine-gamma-Iyase (CSE) inhibitor, DL-propargylglycine or the deendothelization of retinal arteries. Our findings suggested that H2S might play a substantial role in the regulation of retinal arterial tone possibly by acting on K-v and K-ir channels. (C) 2015 Elsevier Ltd. All rights reserved