Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells

Michiya Kida, Toru Sugiyama, Takanobu Yoshimoto, Yoshihiro Ogawa

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H2S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H 2S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H2S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H 2S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H2S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.

Original languageEnglish
Pages (from-to)211-215
Number of pages5
JournalEuropean Journal of Pharmaceutical Sciences
Volume48
Issue number1-2
DOIs
Publication statusPublished - Jan 23 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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