Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo

Toyotaka Yada, Hiroaki Shimokawa, Osamu Hiramatsu, Tatsuya Kajita, Fumiyuki Shigeto, Masami Goto, Yasuo Ogasawara, Fumihiko Kajiya

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)

Abstract

Background - Recent studies in vitro have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans. The aim of this study was to evaluate our hypothesis that endothelium-derived H2O2 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 NG-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 H2O2 into water and oxygen) or tetraethylammonium (TEA, an inhibitor of large-conductance KCa 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 H2O2 is an endogenous EDHF in vivo and plays an important role in coronary autoregulation in cooperation with NO and adenosine.

Original languageEnglish
Pages (from-to)1040-1045
Number of pages6
JournalCirculation
Volume107
Issue number7
DOIs
Publication statusPublished - 2003 Feb 25

Keywords

  • Adenosine
  • Endothelium-derived factors
  • Ischemia
  • Microcirculation
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo'. Together they form a unique fingerprint.

Cite this