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 (H ₂ O ₂ ) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans. The aim of this study was to evaluate our hypothesis that endothelium-derived H ₂ O ₂ 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 (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 H ₂ O ₂ 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 H ₂ O ₂ is an endogenous EDHF in vivo and plays an important role in coronary autoregulation in cooperation with NO and adenosine.