Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart

Ying Jie Chen, Mingxiao Hou, Yunfang Li, Jay H. Traverse, Ping Zhang, Daniela Salvemini, Tohru Fukai, Robert J. Bache

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35 Scopus citations

Abstract

This study examined whether increased superoxide (O2 -.) production contributes to coronary endothelial dysfunction and decreased coronary blood flow (CBF) in congestive heart failure (CHF). To test this hypothesis, the effects of the low-molecular-weight SOD mimetic M40401 on CBF and myocardial oxygen consumption (MV̇o2) were examined in dogs during normal conditions and after CHF was produced by 4 wk of rapid ventricular pacing. The development of CHF was associated with decreases of left ventricular (LV) systolic pressure, maximum first derivative of LV pressure, MV̇o2, and CBF at rest and during treadmill exercise as well as endothelial dysfunction with impaired vasodilation in response to intracoronary acetylcholine. M40401 increased CBF (18 ± 5%, P < 0.01) and MV̇o2 (14 ± 6%, P < 0.01) in CHF dogs and almost totally reversed the impaired CBF response to acetylcholine. M40401 had no effect on acetylcholine-induced coronary vasodilation, CBF, or MV̇o 2 in normal dogs. Western blot analysis demonstrated that extracellular SOD (EC-SOD) was significantly decreased in CHF hearts, whereas mitochondrial Mn-containing SOD was increased. Cytosolic Cu/Zn-containing SOD was unchanged. Both increased O2-.-production and decreased vascular O2-. scavenging ability by EC-SOD could have contributed to endothelial dysfunction in the failing hearts.

Original languageEnglish (US)
Pages (from-to)H133-H141
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

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Keywords

  • Free radicals
  • Myocardium
  • Nitric oxide

ASJC Scopus subject areas

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

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