Hydrogen peroxide as an endothelium-derived hyperpolarizing factor.
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.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi 1-1, Aoba-ku, Sendai, 980-8575, Japan. shimo@cardio.med.tohoku.ac.jp
Hiroaki
H
Shimokawa
D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism
D001685:Biological Factors; D045462:Endothelium-Dependent Relaxing Factors; C067410:endothelium-dependent hyperpolarization factor; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase