Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung

Marc S. Arkovitz, Csaba Szabo, Victor F. Garcia, Hector R. Wong, Jon R. Wispé

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

Original languageEnglish (US)
Pages (from-to)345-350
Number of pages6
JournalShock
Volume7
Issue number5
StatePublished - 1997
Externally publishedYes

Fingerprint

Hyperoxia
Nitric Oxide Synthase
Protein Isoforms
Lung
Nitric Oxide
Lung Injury
Lung Compliance
Arginine
Citrulline
Endothelial Cells
Nitrites
Oxidants
Nitrates
Oxygen
Nitric Oxide Synthase Type III
NG-Nitroarginine Methyl Ester
Bronchoalveolar Lavage Fluid
Nitric Oxide Synthase Type II
Enzymes
Catalysis

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Arkovitz, M. S., Szabo, C., Garcia, V. F., Wong, H. R., & Wispé, J. R. (1997). Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung. Shock, 7(5), 345-350.

Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung. / Arkovitz, Marc S.; Szabo, Csaba; Garcia, Victor F.; Wong, Hector R.; Wispé, Jon R.

In: Shock, Vol. 7, No. 5, 1997, p. 345-350.

Research output: Contribution to journalArticle

Arkovitz, MS, Szabo, C, Garcia, VF, Wong, HR & Wispé, JR 1997, 'Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung', Shock, vol. 7, no. 5, pp. 345-350.
Arkovitz, Marc S. ; Szabo, Csaba ; Garcia, Victor F. ; Wong, Hector R. ; Wispé, Jon R. / Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung. In: Shock. 1997 ; Vol. 7, No. 5. pp. 345-350.
@article{c1c48d2a3b32406a8068fcbb2ac5c867,
title = "Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung",
abstract = "Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.",
author = "Arkovitz, {Marc S.} and Csaba Szabo and Garcia, {Victor F.} and Wong, {Hector R.} and Wisp{\'e}, {Jon R.}",
year = "1997",
language = "English (US)",
volume = "7",
pages = "345--350",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung

AU - Arkovitz, Marc S.

AU - Szabo, Csaba

AU - Garcia, Victor F.

AU - Wong, Hector R.

AU - Wispé, Jon R.

PY - 1997

Y1 - 1997

N2 - Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

AB - Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

UR - http://www.scopus.com/inward/record.url?scp=0031134595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031134595&partnerID=8YFLogxK

M3 - Article

VL - 7

SP - 345

EP - 350

JO - Shock

JF - Shock

SN - 1073-2322

IS - 5

ER -