AUTHOR=Cardounel Arturo J., Julian David , Predmore Benjamin L.

TITLE=Hydrogen Sulfide Increases Nitric Oxide Production from Endothelial Cells by an Akt-Dependent Mechanism

JOURNAL=Frontiers in Physiology

VOLUME=2

YEAR=2011

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2011.00104

DOI=10.3389/fphys.2011.00104

ISSN=1664-042X

ABSTRACT=<p>Hydrogen sulfide (H<sub>2</sub>S) and nitric oxide (NO) are both gasotransmitters that can elicit synergistic vasodilatory responses in the in the cardiovascular system, but the mechanisms behind this synergy are unclear. In the current study we investigated the molecular mechanisms through which H<sub>2</sub>S regulates endothelial NO production. Initial studies were performed to establish the temporal and dose-dependent effects of H<sub>2</sub>S on NO generation using EPR spin trapping techniques. H<sub>2</sub>S stimulated a twofold increase in NO production from endothelial nitric oxide synthase (eNOS), which was maximal 30 min after exposure to 25–150 μM H<sub>2</sub>S. Following 30 min H<sub>2</sub>S exposure, eNOS phosphorylation at Ser 1177 was significantly increased compared to control, consistent with eNOS activation. Pharmacological inhibition of Akt, the kinase responsible for Ser 1177 phosphorylation, attenuated the stimulatory effect of H<sub>2</sub>S on NO production. Taken together, these data demonstrate that H<sub>2</sub>S up-regulates NO production from eNOS through an Akt-dependent mechanism. These results implicate H<sub>2</sub>S in the regulation of NO production in endothelial cells, and suggest that deficiencies in H<sub>2</sub>S signaling can directly impact processes regulated by NO.</p>