Does H2S modulate NO level in cerebral microvascular cells?

Abstract

Hydrogen sulfide (H2S) a newly discovered gasotransmitter, has been reported to cause vasorelaxation via activation of KATP. High level of H2S-synthesizing enzyme, cystathionine-γ-lyase (CSE) has been reported in the brain but its function in the brain microvessels is not well understood. NO plays a significant role in cerebrovascular perfusion and the possibility exist for NO and H2S interactions in the regulation of cerebral function. We have investigated the regulation of NO production by H2S. NO levels were determined in cultured cerebral microvascular cell derived from pig brain following exposure to NaHS (H2S donor), L-cysteine (10−5–10−2 M) a precursor of H2S and a substrate of CSE; in the presence or absence of dl-propargylylglycine (PPG; 10−3M; blocker of CSE). NaHS and L-cysteine differentially regulated NO levels in EC and SMC with NaHS dose-dependently increasing NO level in SMC (7-fold; for 10−2 M) but not in EC. L-Cysteine increased NO level 3-fold in both SMC and EC. Endogenous H2S does not seem to contribute to NaHS-induced NO production in EC or SMC as L-cysteine-induced increased NO level was not affected by CSE inhibition. Thus, these results show a differential and cell-type specific effect of H2S on NO production by SMC and EC with endogenously produced H2S contributing to NO production by SMC but not EC. Further studies are necessary to elucidate the role of H2S in the selective modulation of NO by CMVC as well as the possible contribution of NO to endogenous H2S-induced regulationof cerebrovascular function. This work was supported by grants from NHLBI: HL03674 and HL70669.