Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronary vasodilation in dogs in vivo.

OBJECTIVES We examined whether endogenous hydrogen peroxide (H2O2) is involved in pacing-induced metabolic vasodilation in vivo. BACKGROUND We have previously demonstrated that endothelium-derived H2O2 is an endothelium-derived hyperpolarizing factor in canine coronary microcirculation in vivo. However, the role of endogenous H2O2 in metabolic coronary vasodilation in vivo remains to be examined. METHODS Canine subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) 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 (N(G)-monomethyl-L-arginine [L-NMMA], 2 micromol/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 mug/kg/min for 5 min IC), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA) (K(Ca)-channel blocker, 10 microg/kg/min for 10 min IC), and L-NMMA+catalase+8-SPT. RESULTS Cardiac 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 H2O2 production 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. CONCLUSIONS These results indicate that endogenous H2O2 plays an important role in pacing-induced metabolic coronary vasodilation in vivo.