Important Role of Endogenous Hydrogen Peroxide in Pacing-Induced Metabolic Coronary Vasodilation in Dogs In Vivo

ObjectivesWe examined whether endogenous hydrogen peroxide (H2O2) is involved in pacing-induced metabolic vasodilation in vivo.BackgroundWe have previously demonstrated that endothelium-derived H2O2is an endothelium-derived hyperpolarizing factor in canine coronary microcirculation in vivo. However, the role of endogenous H2O2in metabolic coronary vasodilation in vivo remains to be examined.MethodsCanine subepicardial small coronary arteries (≥100 μm) and arterioles (<100 μm) were continuously observed by a microscope under cyclooxygenase blockade (ibuprofen, 12.5 mg/kg intravenous [IV]) (n = 60). Experiments were performed during paired right ventricular pacing under the following 7 conditions: control, nitric oxide (NO) synthase inhibitor (NG-monomethyl-L-arginine [L-NMMA], 2 μmol/min for 20 min intracoronary [IC]), catalase (a decomposer of H2O2, 40,000 U/kg IV and 240,000 U/kg/min for 10 min IC), 8-sulfophenyltheophylline (SPT) (an adenosine receptor blocker, 25 μg/kg/min for 5 min IC), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA) (KCa-channel blocker, 10 μg/kg/min for 10 min IC), and L-NMMA+catalase+8-SPT.ResultsCardiac tachypacing (60 to 120 beats/min) caused coronary vasodilation in both-sized arteries under control conditions in response to the increase in myocardial oxygen consumption. The metabolic coronary vasodilation was decreased after L-NMMA in subepicardial small arteries with an increased fluorescent H2O2production compared with catalase group, whereas catalase decreased the vasodilation of arterioles with an increased fluorescent NO production compared with the L-NMMA group, and 8-SPT also decreased the vasodilation of arterioles. Furthermore, the metabolic coronary vasodilation was markedly attenuated after L-NMMA+catalase, L-NMMA+TEA, and L-NMMA+catalase+8-SPT in both-sized arteries.ConclusionsThese results indicate that endogenous H2O2plays an important role in pacing-induced metabolic coronary vasodilation in vivo.