Hydrogen peroxide as an endothelium-derived hyperpolarizing factor

Hiroaki Shimokawa

Research output: Contribution to journalReview article

83 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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