Hydrogen peroxide decreases pH(i) in human aortic endothelial cells by inhibiting Na+/H+ exchange

Qinghua Hu, Yong Xia, Stefano Corda, Jay L. Zweier, Roy Ziegelstein

Research output: Contribution to journalArticle

Abstract

Postischemic endothelial dysfunction may occur as a result of the effects of endogenous oxidants like hydrogen peroxide. Since endothelium- dependent vasodilator function may be affected by pH(i), the effect of hydrogen peroxide on endothelial pH(i) was examined. Hydrogen peroxide (100 μmol/L for 10 minutes) decreased phi from 7.24 ± 0.01 to 7.02 ± 0.02 and inhibited recovery from an ammonium chloride-induced intracellular acid load in carboxy SNARF 1 (c-SNARF 1)-loaded human aortic endothelial cells in bicarbonate-free solution. Prior inhibition of Na+/H+ exchange with 5-(N- ethyl-N-isopropyl)amiloride (10 μmol/L), by removal of extracellular Na+, or by glycolytic inhibition with iodoacetic acid blocked the subsequent effect of hydrogen peroxide on pH(i). A 2-minute exposure to 100 μmol/L H2O2 decreased intracellular ATP levels by ≃40%; this was prevented by 3- aminobenzamide and nicotinamide (1 mmol/L each), inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. Both 3-aminobenzamide and nicotinamide significantly inhibited the hydrogen peroxide-induced intracellular acidification and the effect of hydrogen peroxide on recovery from an intracellular acid load. Hydrogen peroxide decreases phi in human endothelial cells by inhibiting Na+/H+ exchange. This appears to be mediated by activation of the DNA repair enzyme poly(ADP-ribose) polymerase and subsequent depletion of intracellular ATP. Since a decrease in phi in this range may alter the activity of NO synthase or affect the synthesis of vasodilator prostaglandins, the effect of hydrogen peroxide on the endothelial Na+/H+ exchanger may be important in the pathogenesis of postischemic endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)644-651
Number of pages8
JournalCirculation Research
Volume83
Issue number6
StatePublished - Sep 21 1998

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Hydrogen Peroxide
Endothelial Cells
DNA Repair Enzymes
Niacinamide
Poly(ADP-ribose) Polymerases
Adenosine Triphosphate
Iodoacetic Acid
Endothelium-Dependent Relaxing Factors
Ammonium Chloride
Sodium-Hydrogen Antiporter
Acids
Bicarbonates
Vasodilator Agents
Oxidants
Nitric Oxide Synthase
Prostaglandins

Keywords

  • Endothelium
  • Free radical
  • Na/H exchange
  • PH(i)

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hydrogen peroxide decreases pH(i) in human aortic endothelial cells by inhibiting Na+/H+ exchange. / Hu, Qinghua; Xia, Yong; Corda, Stefano; Zweier, Jay L.; Ziegelstein, Roy.

In: Circulation Research, Vol. 83, No. 6, 21.09.1998, p. 644-651.

Research output: Contribution to journalArticle

Hu, Qinghua ; Xia, Yong ; Corda, Stefano ; Zweier, Jay L. ; Ziegelstein, Roy. / Hydrogen peroxide decreases pH(i) in human aortic endothelial cells by inhibiting Na+/H+ exchange. In: Circulation Research. 1998 ; Vol. 83, No. 6. pp. 644-651.
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