Published online before print February 3, 2003, doi: 10.1161/01.CIR.0000050145.25589.65
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(Circulation. 2003;107:1040.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Hydrogen Peroxide, an Endogenous Endothelium-Derived Hyperpolarizing Factor, Plays an Important Role in Coronary Autoregulation In Vivo
From the Departments of Medical Engineering and Systems Cardiology, Kawasaki Medical School, Kurashiki (T.Y., O.H., T.K., F.S., M.G., Y.O.); Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka (H.S.); and Cardiovascular Physiology, Okayama University Graduate School of Medicine and Dentistry, Okayama (F.K.), Japan.
Correspondence to Toyotaka Yada, MD, PhD, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan (e-mail yada{at}me.kawasaki-m.ac.jp); reprint requests to Fumihiko Kajiya, MD, PhD, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama, 700-8558, Japan.
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.
Methods and Results— To test this hypothesis, we evaluated vasodilator responses of canine (n=41) subepicardial small coronary arteries (
100 µm) and arterioles (<100 µm) 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 NG-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 KCa 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.
Key Words: endothelium-derived factors • microcirculation • ischemia • nitric oxide • adenosine
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