title: Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide.
abstract: Both nitric oxide (NO) and hydrogen sulfide (H(2)S) are two important gaseous mediators regulating heart function. The present study examined the interaction between these two biological gases and its role in the heart. We found that l-arginine, a substrate of NO synthase, decreased the amplitudes of myocyte contraction and electrically induced calcium transients. Sodium hydrogen sulfide (an H(2)S donor), which alone had minor effect, reversed the negative inotropic effects of l-arginine. The effect of l-arginine + sodium hydrogen sulfide was abolished by three thiols (l-cysteine, N-acetyl-cysteine, and glutathione), suggesting that the effect of H(2)S + NO is thiol sensitive. The stimulatory effect on heart contractility was also induced by GYY4137, a slow-releasing H(2)S donor, when used together with sodium nitroprusside, an NO-releasing donor. More importantly, enzymatic generation of H(2)S from recombinant cystathionine-γ-lyase protein also interacted with endogenous NO generated from l-arginine to stimulate heart contraction. In summary, our data suggest that endogenous NO may interact with H(2)S to produce a new biological mediator that produces positive inotropic effect. The crosstalk between H(2)S and NO also suggests an intriguing potential for the endogenous formation of a thiol-sensitive molecule, which may be of physiological significance in the heart.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Qian-Chen
authors.initials: QC
authors.lastname: Yong
authors.forename: Jia Ling
authors.initials: JL
authors.lastname: Cheong
authors.forename: Fei
authors.initials: F
authors.lastname: Hua
authors.forename: Lih-Wen
authors.initials: LW
authors.lastname: Deng
authors.forename: Yok Moi
authors.initials: YM
authors.lastname: Khoo
authors.forename: How-Sung
authors.initials: HS
authors.lastname: Lee
authors.forename: Alexis
authors.initials: A
authors.lastname: Perry
authors.forename: Mark
authors.initials: M
authors.lastname: Wood
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003864:Depression, Chemical; D004558:Electric Stimulation; D005740:Gases; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D005740:Gases; D009569:Nitric Oxide; D002110:Caffeine; D001120:Arginine; D006862:Hydrogen Sulfide