Hydrogen peroxide as an endothelium-derived hyperpolarizing factor

Hiroaki Shimokawa

Research output: Contribution to journalReview articlepeer-review

93 Citations (Scopus)


The endothelium plays an important role in maintaining cardiovascular homeostasis by synthesizing and releasing several vasodilating substances, including vasodilator prostaglandins, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Since the first report on the existence of EDHF, several substances/mechanisms have been proposed for the nature of EDHF, including epoxyeicosatrienoic acids (metabolites of arachidonic P450 epoxygenase pathway), K ions, and electrical communications through myoendothelial gap junctions. We have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans. For the synthesis of H2O2/EDHF, endothelial NO synthase system that is functionally coupled with Cu,Zn-superoxide dismutase plays a crucial role. Importantly, endothelium-derived H2O2 plays important protective roles in the coronary circulation, including coronary autoregulation, protection against myocardial ischemia/reperfusion injury, and metabolic coronary vasodilatation. Indeed, our H2O2/EDHF theory demonstrates that endothelium-derived H2O2, another reactive oxygen species in addition to NO, plays important roles as a redox-signaling molecule to cause vasodilatation as well as cardioprotection. In this review, we summarize our current knowledge on H2O 2/EDHF regarding its identification and mechanisms of synthesis and actions.

Original languageEnglish
Pages (from-to)915-922
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Issue number6
Publication statusPublished - 2010 May


  • Atherosclerosis
  • Endothelium-derived hyperpolarizing factor
  • Endothelium-derived relaxing factors
  • Oxygen radical
  • Vasodilatation
  • Vasomotion

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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