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Hydrogen peroxide as an endothelium-derived hyperpolarizing factor

  • Cardiovascular Physiology
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Abstract

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 H2O2/EDHF regarding its identification and mechanisms of synthesis and actions.

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Acknowledgments

The authors wish to thank the following collaborators for their cooperation: Drs. A. Takaki and J. Ohashi at Tohoku University, Morikawa K, T. Matoba, and A. Takeshita at Kyushu University, Dr. M. Tsutsui at Ryukyu University, and Drs. T. Yada and F. Kajiya at Kawasaki University. The authors’ works were supported in part by the grants from the Japanese Ministry of Education, Science, Sports, and Culture, Tokyo, Japan.

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  1. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Aoba-ku, Sendai, 980-8575, Japan

    Hiroaki Shimokawa

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Correspondence to Hiroaki Shimokawa.

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H2O2 as an EDHF.

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Shimokawa, H. Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pflugers Arch - Eur J Physiol 459, 915–922 (2010). https://doi.org/10.1007/s00424-010-0790-8

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