title: Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo.
abstract: BACKGROUND
  Recent studies in vitro have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans. The aim of this study was to evaluate our hypothesis that endothelium-derived H2O2 is an EDHF in vivo and plays an important role in coronary autoregulation.
  
  
  RESULTS
  To test this hypothesis, we evaluated vasodilator responses of canine (n=41) subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) with an intravital microscope in response to acetylcholine and to a stepwise reduction in coronary perfusion pressure (from 100 to 30 mm Hg) before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA). After L-NMMA, the coronary vasodilator responses were attenuated primarily in small arteries, whereas combined infusion of L-NMMA plus catalase (an enzyme that selectively dismutates H2O2 into water and oxygen) or tetraethylammonium (TEA, an inhibitor of large-conductance K(Ca) channels) attenuated the vasodilator responses of coronary arteries of both sizes. Residual arteriolar dilation after L-NMMA plus catalase or TEA was largely attenuated by 8-sulfophenyltheophylline, an adenosine receptor inhibitor.
  
  
  CONCLUSIONS
  These results suggest that H2O2 is an endogenous EDHF in vivo and plays an important role in coronary autoregulation in cooperation with NO and adenosine.
authors.affiliation: Department of Medical Engineering, Kawasaki Medical School, Kurashiki, Okayama, Japan. yada@me.kawasaki-m.ac.jp
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Yada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Hiramatsu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kajita
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Shigeto
authors.forename: Masami
authors.initials: M
authors.lastname: Goto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kajiya
mesh_terms: D000241:Adenosine / Q000097:blood; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D025461:Feedback, Physiological; D005260:Female; D006439:Hemodynamics; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D017202:Myocardial Ischemia / Q000209:etiology; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D014664:Vasodilation
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D002245:Carbon Dioxide; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000241:Adenosine; D010100:Oxygen