Hydrogen peroxide as an endothelium-derived hyperpolarizing factor

Hiroaki Shimokawa, Tetsuya Matoba

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)


Vascular endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, such as prostacyclin, nitric oxide (NO), and a yet unidentified endothelium-derived hyperpolarizing factor (EDHF). Possible candidates for EDHF include epoxyeicosatrienoic acids (EETs), endothelium-derived potassium ions (K +), and as we have recently identified, hydrogen peroxide (H 2O2). Electrical communication between endothelial and smooth muscle cells through gap junctions has also been suggested to be involved in endothelium-dependent hyperpolarization. Among the above candidates, the H2O2 hypothesis well explains the pathophysiological interactions between NO and EDHF and re-highlights the physiological roles of the reactive oxygen species (ROS) in endothelium-dependent vascular responses. This brief review summarizes our current knowledge about H2O 2 as an EDHF, with special reference to its production by the endothelium, its action on membrane potentials and its pathophysiological roles.

Original languageEnglish
Pages (from-to)543-549
Number of pages7
JournalPharmacological Research
Issue number6
Publication statusPublished - Jun 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology


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