Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide

Autor: Jin-Song Bian, Lih-Wen Deng, Fei Hua, Matthew Whiteman, Qian Chen Yong, Jia Ling Cheong, Alexis Perry, How Sung Lee, Yok Moi Khoo, Mark E. Wood
Rok vydání: 2011
Předmět:
Zdroj: Antioxidantsredox signaling. 14(11)
ISSN: 1557-7716
Popis: 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.
Databáze: OpenAIRE