Pharmacological actions of the slow release hydrogen sulfide donor GYY4137 on phenylephrine-induced tone in isolated bovine ciliary artery

Hydrogen sulfide (H₂S), a colorless gas characterized by its pungent odor of rotten eggs has been reported to elicit relaxation effects on basal and pre-contracted non-ocular smooth muscles of several mammalian species. In the present study, we investigated the pharmacological actions of a H₂S donor, GYY4137 on isolated bovine posterior ciliary artery after contraction with the adrenergic receptor agonist, phenylephrine. Furthermore, we studied the underlying mechanism of inhibitory action of GYY4137 on the posterior ciliary arteries. Isolated bovine posterior ciliary arteries were mounted in oxygenated organ baths and changes in isometric tension were measured with a Grass FT03 transducer connected to a recorder using a Grass Polyview Software. The relaxant actions of GYY4137 on phenylephrine pre-contracted arteries were observed in the absence and presence of an inhibitor of cyclo-oxygenase, flurbiprofen. Furthermore, the inhibitory effects of GYY4137 were studied in the absence or presence of inhibitors/activators of biosynthetic enzymes for H₂S and nitric oxide production, as well as specific ion channel blockers. In the concentration range, 100nM to 100μM, GYY4137 elicited a concentration-dependant relaxation of phenylephrine-induced tone in isolated posterior ciliary arteries, with IC₅₀ value of 13.4±1.9μM (n=6). The cyclo-oxygenase inhibitor, flurbiprofen, significantly (p50 value of 0.13±0.08μM (n=6). Both the inhibitors of cystathionine β-synthase (aminooxyacetic acid, AOAA, 30μM) and cystathionine γ-lyase (propargylglycine, PAG, 1mM) caused significant (pATP channel antagonist, glibenclamide (100μM) significantly (p2S. Furthermore, the observed vascular smooth muscle relaxation induced by GYY4137 is mediated, at least in part, by K_ATP channels.