Involvement of hydrogen sulfide in perivascular and hypoxia-induced inhibition of endothelin contraction in porcine retinal arterioles.

ABSTRACT

Perivascular retina has been shown to regulate retinal vascular tone. In the present study, we evaluated an ex vivo retina preparation, and investigated whether hydrogen sulfide (H2S) mediates an inhibitory effect of retina and/or hypoxia on arteriolar tone. In retina, immunolabeling showed an increase of glial fibrillary acidic protein, but not vimentin over time in Müller cells, and the presence of necrotic cells after 2 h and apoptotic cells after 8 h. Isometric tension recordings showed endothelin-1(ET-1) to induce concentration-dependent contractions, which were reduced in the presence of retina. In arterioles with retina no change was observed in ET-1 contractions after 5 h compared to 8 h. Hypoxia (1% O2) reduced ET-1 contraction in arterioles with and without retina. The H2S donor, GYY4137 and the salt, sodium hydrogen sulfide, induced concentration-dependent relaxations in ET-1 contracted retinal arterioles. Inhibition of the H2S producing enzymes, cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), with carboxymethoxylamine (AOA) and L-propargylglycine (PPG) enhanced ET-1 contractions. This effect was more pronounced in hypoxic conditions. However, even in the presence of AOA and PPG ET-1 induced less contraction in the presence of perivascular retina compared to isolated vessels. These findings suggest that both the presence of perivascular retina and hypoxia reduce arteriolar vasoconstriction and that both H2S and another factor mediate this effect. Finally, H2S donors, as well as endogenous H2S, can reduce retinal arteriolar tone, suggesting a potential therapeutic role for enhanced H2S bioavailability in the treatment of retinal disease.