title: Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.
abstract: This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S 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 H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S 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 H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Health Science Research Facility Building, Burlington, VT 05405, USA. george.webb@uvm.edu
authors.forename: George D
authors.initials: GD
authors.lastname: Webb
authors.forename: Lay Har
authors.initials: LH
authors.lastname: Lim
authors.forename: Vernon M S
authors.initials: VM
authors.lastname: Oh
authors.forename: Soh Bee
authors.initials: SB
authors.lastname: Yeo
authors.forename: Yoke Ping
authors.initials: YP
authors.lastname: Cheong
authors.forename: Muhammed Yusuf
authors.initials: MY
authors.lastname: Ali
authors.forename: Reida
authors.initials: R
authors.lastname: El Oakley
authors.forename: Chuen Neng
authors.initials: CN
authors.lastname: Lee
authors.forename: Poo Sing
authors.initials: PS
authors.lastname: Wong
authors.forename: Michael G
authors.initials: MG
authors.lastname: Caleb
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
authors.forename: Edwin S Y
authors.initials: ES
authors.lastname: Chan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Taylor
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008323:Mammary Arteries / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide