Hydrogen Peroxide As an Endothelium-derived Hyperpolarizing Factor

Overview

Journal Pflugers Arch

Specialty Physiology

Date 2010 Feb 9

PMID 20140449

Citations 49

Authors

Hiroaki Shimokawa

Affiliations

Soon will be listed here.

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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