Hydrogen peroxide as an endothelium-derived hyperpolarizing factor - PubMed (original) (raw)

Review

. 2010 May;459(6):915-22.

doi: 10.1007/s00424-010-0790-8. Epub 2010 Feb 6.

Affiliations

• PMID: 20140449
• DOI: 10.1007/s00424-010-0790-8

Review

Hydrogen peroxide as an endothelium-derived hyperpolarizing factor

Hiroaki Shimokawa. Pflugers Arch. 2010 May.

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 (H(2)O(2)) is an EDHF in animals and humans. For the synthesis of H(2)O(2)/EDHF, endothelial NO synthase system that is functionally coupled with Cu,Zn-superoxide dismutase plays a crucial role. Importantly, endothelium-derived H(2)O(2) plays important protective roles in the coronary circulation, including coronary autoregulation, protection against myocardial ischemia/reperfusion injury, and metabolic coronary vasodilatation. Indeed, our H(2)O(2)/EDHF theory demonstrates that endothelium-derived H(2)O(2), 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 H(2)O(2)/EDHF regarding its identification and mechanisms of synthesis and actions.

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