Abstract
Purpose: :
We have evidence that hydrogen sulfide (H2S) donors can exert pharmacological effects on various mammalian ocular tissues (Opere CA et al., 2009; Neurochem Res. 34:1962-68; Ohia, SE et al., 2010; Curr Eye 3:402-407). In the present study, we investigated the pharmacological action of H2S donors, sodium hydrosulfide (NaHS), sodium sulfide (Na2S), and substrate, L-cysteine on isolated bovine ciliary artery.
Methods: :
Posterior ciliary arteries were removed from freshly excised bovine eyeballs and set up in organ baths containing oxygenated Krebs solution. Changes in isometric tension were displayed on a computer using the Grass PolyView software. The effects of NaHS, Na2S and L-cysteine were studied in the absence or presence of various inhibitors or activator of enzymes involved in H2S biosynthesis or cyclooxygenase (COX) inhibition. Furthermore, we examined the effects of KATP channel antagonist, glibenclamide and nitric oxide (NO) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) on H2S donor/substrate-induced response.
Results: :
Both NaHS (1 nM-100 µM) and Na2S (1 nM-30 µM) elicited concentration-dependent relaxation of basal tone in bovine ciliary artery. Likewise, L-cysteine (10 nM-100 µM) also elicited a concentration-dependent relaxation of basal tone in ciliary artery. Inhibitors of cystathionine γ-lyase (CSE; proparglyglycine, 1 mM) and cystathionine β-synthase (CBS; aminooxyacetic acid, 30 µM) significantly (p<0.01) reduced the relaxation of ciliary artery induced by L-cysteine. On the other hand, the activator of CBS, S-adenosylmethionine (100 µM) significantly (p<0.01) enhanced the relaxation of ciliary artery induced by L-cysteine. The KATP channel antagonist, glibenclamide (100 µM) significantly (p<0.001) attenuated the relaxation of ciliary artery induced by NaHS. However, the COX inhibitors, flurbiprofen (3 µM) and indomethacin (10 µM) had no significant effect on relaxation induced by both NaHS and Na2S. Similarly, the NO inhibitor, L-NAME (100 µM) had no significant effect on L-cysteine-induced relaxation of ciliary artery.
Conclusions: :
Intramural generation of H2S elicited by donors or substrate induced relaxation of basal tone in isolated bovine posterior ciliary artery. Vascular relaxations induced by increased production of this gas was blocked or enhanced by enzyme inhibitors/activator. Furthermore, H2S-induced relaxations of these blood vessels are mediated, at least in part, through an action of KATP channel.