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Madhura S. Kulkarni, Ya Fatou Njie-Mbye, Catherine A. Opere, Matt Whiteman, Sunny E. Ohia; Effect of Slow Releasing Hydrogen Sulfide Donor GYY4137 on Isolated Bovine Ciliary Artery. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6866.
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© ARVO (1962-2015); The Authors (2016-present)
Hydrogen sulfide (H2S), a colorless gas characterized by its pungent odor of rotten eggs has been reported to elicit relaxation effects on non-ocular smooth muscles of several mammalian species. The purpose of the present study is to investigate whether the slow releasing H2S donor, GYY4137 can induce pharmacological actions on isolated bovine ciliary artery.
Isolated bovine posterior ciliary arteries were set up in 25 mL organ baths containing oxygenated Krebs solution (pH 7.4) at 370 C. Changes in longitudinal isometric tension were recorded via a grass FT03 Force-displacement Transducers and analyzed using the Grass PolyView computer software. The relaxant action of GYY 4137 on phenylephrine induced tone was studied in the absence or presence of inhibitors of enzymes for the biosynthetic pathways of H2S and prostanoids. In addition, we examined the effects of ATP-sensitive K+ (KATP) channel antagonist, glibenclamide on GYY4137 induced response.
The slow releasing H2S donor, GYY4137 (10nM-0.1µM) elicited a concentration-dependent relaxation of phenylephrine induced tone in bovine ciliary artery. This response was significantly (P<0.05) enhanced in the presence of the cyclo-oxygenase inhibitor, flurbiprofen (3μM). Other H2S donors (MC05, MC06 and sodium hydrosulfide (NaHS) also exerted similar response in the following order of magnitude; MC06>NaHS>GYY4137>MC05. Interestingly, the inhibitor of cystathionine β-synthase, AOA (30µM) caused a rightward shift in the concentration-response curve to GYY4137 whilst, the inhibitor of cystathionine γ-lyase, PAG (1mM) only attenuated relaxations caused by high concentrations of GYY4137 (>1µM). The KATP channel antagonist, glibenclamide (100µM) did not affect the relaxation action induced by GYY4137 on ciliary artery.
The slow releasing H2S donor, GYY4137 can relax isolated bovine ciliary artery, an effect dependant on endogenous production of H2S. Prostanoids are involved in the inhibitory action of GYY4137. The observed vascular relaxation induced by GYY 4137 suggest that slow releasing H2S molecules might serve as potential therapeutic agents to increase ocular blood flow, consequently preserving the optic nerve and alleviating vision loss.
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