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, Tomomi Ide, Hiroyuki Tsutsui, Hiroaki Shimokawa, Akira Takeshita

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number6 50-6
Publication statusPublished - Dec 1 2001

Fingerprint

Nitric Oxide
Heart Failure
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Reactive Oxygen Species
Free Radicals
Dogs
omega-N-Methylarginine
Adenosine
Ischemia
Antioxidants
Free Radical Scavengers
Lipid Peroxides
Electron Spin Resonance Spectroscopy
Nitroprusside
Microvessels
Tachycardia
Vasodilation
Canidae
Staining and Labeling

All Science Journal Classification (ASJC) codes

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

Cite this

Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure. / Nakamura, R. Y.O.; Egashira, Kensuke; Arimura, Kenichi; Machida, Youji; Ide, Tomomi; Tsutsui, Hiroyuki; Shimokawa, Hiroaki; Takeshita, Akira.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 281, No. 6 50-6, 01.12.2001.

Research output: Contribution to journalArticle

@article{f5a4a44aec034b4685df2dbd1692513d,
title = "Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure",
abstract = "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.",
author = "Nakamura, {R. Y.O.} and Kensuke Egashira and Kenichi Arimura and Youji Machida and Tomomi Ide and Hiroyuki Tsutsui and Hiroaki Shimokawa and Akira Takeshita",
year = "2001",
month = "12",
day = "1",
language = "English",
volume = "281",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6 50-6",

}

TY - JOUR

T1 - Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure

AU - Nakamura, R. Y.O.

AU - Egashira, Kensuke

AU - Arimura, Kenichi

AU - Machida, Youji

AU - Ide, Tomomi

AU - Tsutsui, Hiroyuki

AU - Shimokawa, Hiroaki

AU - Takeshita, Akira

PY - 2001/12/1

Y1 - 2001/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035658484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035658484&partnerID=8YFLogxK

M3 - Article

C2 - 11709431

AN - SCOPUS:0035658484

VL - 281

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 6 50-6

ER -