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

Abstract

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.