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Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury.

Publication ,  Journal Article
Huang, YC; Fisher, PW; Nozik-Grayck, E; Piantadosi, CA
Published in: Am J Physiol
September 1997

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

September 1997

Volume

273

Issue

3 Pt 1

Start / End Page

L504 / L512

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Superoxide Dismutase
  • Stereoisomerism
  • Reperfusion Injury
  • Rabbits
  • Pulmonary Circulation
  • Pulmonary Artery
  • Nitric Oxide Synthase
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester
 

Citation

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MLA
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Huang, Y. C., Fisher, P. W., Nozik-Grayck, E., & Piantadosi, C. A. (1997). Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury. Am J Physiol, 273(3 Pt 1), L504–L512. https://doi.org/10.1152/ajplung.1997.273.3.L504
Huang, Y. C., P. W. Fisher, E. Nozik-Grayck, and C. A. Piantadosi. “Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury.Am J Physiol 273, no. 3 Pt 1 (September 1997): L504–12. https://doi.org/10.1152/ajplung.1997.273.3.L504.
Huang YC, Fisher PW, Nozik-Grayck E, Piantadosi CA. Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury. Am J Physiol. 1997 Sep;273(3 Pt 1):L504–12.
Huang, Y. C., et al. “Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury.Am J Physiol, vol. 273, no. 3 Pt 1, Sept. 1997, pp. L504–12. Pubmed, doi:10.1152/ajplung.1997.273.3.L504.
Huang YC, Fisher PW, Nozik-Grayck E, Piantadosi CA. Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury. Am J Physiol. 1997 Sep;273(3 Pt 1):L504–L512.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

September 1997

Volume

273

Issue

3 Pt 1

Start / End Page

L504 / L512

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Superoxide Dismutase
  • Stereoisomerism
  • Reperfusion Injury
  • Rabbits
  • Pulmonary Circulation
  • Pulmonary Artery
  • Nitric Oxide Synthase
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester