title: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in animals and humans.
abstract: The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating substances, including vasodilator prostaglandins, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Since the first report for 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 recently demonstrated that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in mouse and human mesenteric arteries and in porcine coronary microvessels. For the synthesis of H(2)O(2) as an EDHF, endothelial Cu,Zn-superoxide dismutase plays an important role in mesenteric arteries of mice and humans. We also have demonstrated that EDHF-mediated responses are attenuated by several arteriosclerotic risk factors, including diabetes mellitus and hyperlipidemia and their combination in particular. Recent studies have indicated that endothelium-derived H(2)O(2) plays an important protective role in coronary autoregulation and myocardial ischemia/reperfusion injury in vivo. 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 an important role as a redox signaling molecule to cause vasodilatation as well as cardioprotection. In this review, we summarize our knowledge on H(2)O(2)/EDHF regarding its identification, mechanisms of synthesis, and clinical implications.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. shimo@cardio.med.tohoku.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014665:Vasodilator Agents
chemical_list: D001685:Biological Factors; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D006861:Hydrogen Peroxide