title: Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronary vasodilation in dogs in vivo.
abstract: OBJECTIVE
  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.
authors: Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, Kurashiki, Okayama, Japan. yada@me.kawasaki-m.ac.jp
authors: Toyotaka
authors: T
authors: Yada
authors: Hiroaki
authors: H
authors: Shimokawa
authors: Osamu
authors: O
authors: Hiramatsu
authors: Yoshiro
authors: Y
authors: Shinozaki
authors: Hidezo
authors: H
authors: Mori
authors: Masami
authors: M
authors: Goto
authors: Yasuo
authors: Y
authors: Ogasawara
authors: Fumihiko
authors: F
authors: Kajiya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D002374:Catalase / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010101:Oxygen Consumption; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019789:Tetraethylammonium; C031433:8-(4-sulfophenyl)theophylline; D006861:Hydrogen Peroxide; D013806:Theophylline; D002374:Catalase; D007052:Ibuprofen