Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure

R. Y.O. Nakamura, Kensuke Egashira, Kenichi Arimura, Youji Machida, I. D.E. Tomomi, Hiroyuki Tsutsui, Hiroaki Shimokawa, Akira Takeshita

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20 Citations (Scopus)


Recent evidence suggests that increased inactivation of endothelium-derived nitric oxide (NO) by oxygen free radical (OFR) formation is involved in the pathogenesis of endothelial dysfunction in heart failure (HF). However, it is unclear whether increased OFR limits coronary flow reserve in HF. To test this hypothesis, we examined the effects of antioxidant therapy on coronary flow reserve in a canine model of tachycardia-induced HF. The flow reserve (percent increase in coronary blood flow) to adenosine or to 20-s ischemia was less and OFR formation (electron-spin resonance spectroscopy) in myocardial tissues was greater in HF dogs than in controls. Immunohistochemical staining of 4-hydroxy-2-nonenal, an OFR-induced lipid peroxide, was detected in coronary microvessels of HF dogs. Intracoronary infusion of a cell-permeable OFR scavenger, tiron, suppressed OFR formation and improved the vasodilating capacity to adenosine or brief ischemia in HF dogs but not in controls. A NO synthesis inhibitor, NG-monomethyl-Larginine (L-NMMA), diminished the beneficial effects of tiron in HF dogs. Vasodilation to sodium nitroprusside was similar between control and HF dogs, and no change in its response was noted with tiron or tiron + L-NMMA in either group. In summary, antioxidant treatment with tiron improved coronary flow reserve by increasing NO bioactivity in HF dogs. Thus increased OFR formation may impair coronary flow reserve in HF by reducing NO bioactivity.

Original languageEnglish
Pages (from-to)H2619-H2625
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 50-6
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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