Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery

G.D. Webb, L.H. Lim, V.M.S. Oh, S.B. Yeo, Y.P. Cheong, M.Y. Ali, R. El Oakley, C.N. Lee, P.S. Wong, M.G. Caleb, Manuel Salto-Tellez, M. Bhatia, E.S.Y. Chan, E.A. Taylor, P.K. Moore

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

This study aimed to test these hypotheses: cystathionine gamma-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 K-ATP 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 K-ATP 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.
Original languageEnglish
Pages (from-to)876-882
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume324
Issue number2
DOIs
Publication statusPublished - Feb 2008

ASJC Scopus subject areas

  • Pharmacology

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