Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo.
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.
Yada
Toyotaka
T
Department of Medical Engineering, Kawasaki Medical School, Kurashiki, Okayama, Japan. yada@me.kawasaki-m.ac.jp
Shimokawa
Hiroaki
H
Hiramatsu
Osamu
O
Kajita
Tatsuya
T
Shigeto
Fumiyuki
F
Goto
Masami
M
Ogasawara
Yasuo
Y
Kajiya
Fumihiko
F
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
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D002245:Carbon Dioxide; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000241:Adenosine; D010100:Oxygen