Abstract
This study aimed to test these hypotheses: cystathionine γ-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H2S), and H2S relaxes a human artery. H2S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H2S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H2S, and the H2S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H2S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of KATP channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H2S, and that higher concentrations of H2S relax human arteries, in part by opening KATP channels. Low concentrations of H2S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H2S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.
Footnotes
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The Agency for Science, Technology and Research (A*STAR) awarded a Graduate Scholarship to M.Y.A., and the Office of Life Science of the National University of Singapore (Grant R-184-000-074-712) provided the financial support for this project (principal investigator, P.K.M.) Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.133538.
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ABBREVIATIONS: H2S, hydrogen sulfide; NaHS, sodium hydrogen sulfide, but often called sodium hydrosulfide; CSE, cystathionine γ-lyase; RT, reverse transcription; PCR, polymerase chain reaction; HSP, heat shock protein; PAG, dl-propargylglycine; PE, phenylephrine; Ach, acetylcholine; PE, phenylephrine; NOS, nitric-oxide synthase.
- Received October 24, 2007.
- Accepted November 19, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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