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Hydrogen sulfide: A novel gasotransmitter that prevents postischemic leukocyte‐endothelial interactions
Author(s) -
Yusof M,
Kamada K,
Gaskin F,
Korthuis R J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a291-c
Subject(s) - nitric oxide , chemistry , enos , pharmacology , nitric oxide synthase , ingestion , ischemia , biochemistry , medicine , organic chemistry
We previously demonstrated that consuming low levels of ethanol (EtOH) 24 hr prior to ischemia/reperfusion (I/R) prevents postischemic leukocyte‐endothelial interactions (LEI) by a nitric oxide (NO)‐initiated mechanism. Since NO acts endogenously as a regulator of a second gasotransmitter, hydrogen sulfide (H 2 S), we postulated that H 2 S may also play a role in triggering the anti‐inflammatory phenotype induced by antecedent EtOH ingestion. EtOH was administered to C57BL/6 mice by gavage at a dose that produced a peak plasma concentration of 45 mg/dl 30 min after ingestion. 24 hr later, LEI in small intestinal postcapillary venules were recorded using an intravital microscopic approach. Pharmacologic inhibition of the predominant H 2 S producing enzyme in the vasculature, cystathionine γ‐lyase (CSE), by propargylglycine or β‐cyanoalanine, did not attenuate the beneficial anti‐adhesive actions of EtOH. However, the postischemic increase in LEI was prevented by preconditioning with an H 2 S donor, NaHS. The reduction in leukocyte rolling induced by H 2 S preconditioning was inhibited by treatment with the NO synthase inhibitor, L‐NIO, in WT animals and was attenuated in eNOS‐/‐ mice. Although our results suggest that the anti‐inflammatory effects of EtOH ingestion do not occur by a CSE‐dependent mechanism, our data does provide the first evidence that H 2 S can function as a preconditioning stimulus and prevent I/R‐induced LEI. Our work suggests that a novel class of agents, H 2 S donors, may represent a new avenue for therapeutic intervention in I/R. Supported by NIH grant DK 43785.