Abstract
Purpose:
Hydrogen sulfide (H2S) has been reported to cause relaxation of both ocular and non-ocular smooth muscles of several mammalian species. The aim of present study was to investigate whether two novel H2S donors, AP67 {(4-methoxyphenyl)pyrrolidin-1-ylphosphinodithioc acid} and AP72 {(4-methoxyphenyl)piperidin-1-ylphosphinodithioc acid)} can induce pharmacological actions on isolated bovine ciliary artery.
Methods:
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 Grass FT03 Force-displacement Transducers and analyzed using the Grass PolyView computer software. The relaxant effect of AP67 and AP72 on phenylephrine-induced tone was studied in the absence or presence of inhibitors of enzymes for the biosynthetic pathways of H2S, nitric oxide and prostanoids. In addition, we examined the effects of ATP-sensitive K+ (KATP) channel antagonist, glibenclamide on relaxations induced by AP67 and AP72.
Results:
Both AP67 (1 nM - 10 µM) and AP72 (10 nM - 1 µM) elicited a concentration-dependent relaxation of phenylephrine-induced tone in bovine ciliary artery. While the COX inhibitor, flurbiprofen (3 µM) blocked significantly (p < 0.05) the inhibitory response elicited by AP67, it had no effect on relaxations induced by AP72. Both the inhibitors of cystathionine β-synthase (aminooxyacetic acid, 30 μM) and cystathionine γ-lyase (propargylglycine, 1 mM) caused significant (p<0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the KATPchannel antagonist, glibenclamide (100 µM) and the nitric oxide synthase inhibitor, L-NAME (100 µM) significantly attenuated (p<0.05) the relaxation effect induced by AP67 and AP72 on ciliary artery.
Conclusions:
The H2S donors, AP67 and AP72 can relax precontracted isolated bovine ciliary artery, an effect dependant on endogenous production of H2S. The inhibitory action of AP67 (but not that of AP72) on pre-contracted ciliary artery may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H2S donors on ciliary arteries may also depend, at least in part, on the endogenous biosynthesis of NO and by an action of KATP channels.
Keywords: 615 neuroprotection •
628 optic flow •
436 blood supply