Does H2S modulate NO level in cerebral microvascular cells?

Hydrogen sulfide (H 2 S) a newly discovered gasotransmitter, has been reported to cause vasorelaxation via activation of K ATP . High level of H 2 S‐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 H 2 S interactions in the regulation of cerebral function. We have investigated the regulation of NO production by H 2 S. NO levels were determined in cultured cerebral microvascular cell derived from pig brain following exposure to NaHS (H 2 S donor), L‐cysteine (10 −5 –10 −2 M) a precursor of H 2 S and a substrate of CSE; in the presence or absence of dl ‐propargylylglycine (PPG; 10 −3 M; 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 H 2 S 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 H 2 S on NO production by SMC and EC with endogenously produced H 2 S contributing to NO production by SMC but not EC. Further studies are necessary to elucidate the role of H 2 S in the selective modulation of NO by CMVC as well as the possible contribution of NO to endogenous H 2 S‐induced regulationof cerebrovascular function. This work was supported by grants from NHLBI: HL03674 and HL70669.