Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity

Mariarosaria Bucci, Andreas Papapetropoulos, Valentina Vellecco, Zongmin Zhou, Anastasia Pyriochou, Charis Roussos, Fiorentina Roviezzo, Vincenzo Brancaleone, Giuseppe Cirino

Research output: Contribution to journalArticle

197 Scopus citations

Abstract

Objective-: Recent studies have demonstrated that hydrogen sulfide (H 2S) is produced within the vessel wall from l-cysteine regulating several aspects of vascular homeostasis. H2S generated from cystathione γ-lyase (CSE) contributes to vascular tone; however, the molecular mechanisms underlying the vasorelaxing effects of H2S are still under investigation. Methods and results-: Using isolated aortic rings, we observed that addition of l-cysteine led to a concentration-dependent relaxation that was prevented by the CSE inhibitors dl-propargylglyicine (PAG) and β-cyano-l-alanine (BCA). Moreover, incubation with PAG or BCA resulted in a rightward shift in sodium nitroprusside-and isoproterenol-induced relaxation. Aortic tissues exposed to PAG or BCA contained lower levels of cGMP, exposure of cells to exogenous H2S or overexpression of CSE raised cGMP concentration. RNA silencing of CSE expression reduced intracellular cGMP levels confirming a positive role for endogenous H2S on cGMP accumulation. The ability of H2S to enhance cGMP levels was greatly reduced by the nonselective phosphodiesterase inhibitor 3-isobutyl-1- methylxanthine. Finally, addition of H2S to a cell-free system inhibited both cGMP and cAMP breakdown. Conclusion-: These findings provide direct evidence that H2S acts as an endogenous inhibitor of phosphodiesterase activity and reinforce the notion that this gasotransmitter could be therapeutically exploited.

Original languageEnglish (US)
Pages (from-to)1998-2004
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number10
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Keywords

  • cAMP
  • cGMP
  • cystathioneγ-lyase
  • endothelium
  • hydrogen sulfide
  • hypertension
  • phosphodiesterase
  • signal transduction
  • vascular muscle
  • vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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    Bucci, M., Papapetropoulos, A., Vellecco, V., Zhou, Z., Pyriochou, A., Roussos, C., Roviezzo, F., Brancaleone, V., & Cirino, G. (2010). Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity. Arteriosclerosis, thrombosis, and vascular biology, 30(10), 1998-2004. https://doi.org/10.1161/ATVBAHA.110.209783