In a canine model (n=41), combined infusion of L-NMMA plus catalase or TEA attenuated coronary vasodilator responses to perfusion pressure reduction (100 to 30 mm Hg), indicating H2O2 is an EDHF.
Hydrogen peroxide acts as an endogenous endothelium-derived hyperpolarizing factor in vivo, playing a key role in coronary autoregulation alongside NO and adenosine.
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 (<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 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.
Yada et al. (2003) studied Coronary autoregulation (n=41). L-NMMA plus catalase or TEA vs. L-NMMA alone / baseline was evaluated on Vasodilator responses to acetylcholine and stepwise reduction in coronary perfusion pressure. In a canine model (n=41), combined infusion of L-NMMA plus catalase or TEA attenuated coronary vasodilator responses to perfusion pressure reduction (100 to 30 mm Hg), indicating H2O2 is an EDHF.