NOS and COX isoforms and abnormal microvessel responses to CO2 and H+ in hyperoxia-injured lungs

K. Naoki, H. Kudo, K. Suzuki, K. Takeshita, N. Miyao, M. Ishii, N. Sato, Y. Suzuki, H. Tsumura, K. Yamaguchi

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3 Citations (Scopus)

Abstract

The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). Real-time confocal luminescence microscopy was used to measure changes in the diameter of acinar arterioles, venules and capillaries in response to stimulation with hypercapnic and isocapnic acidosis in isolated rat lungs injured by 90% oxygen exposure for 48 h. Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX-1) and inducible isoforms (iNOS and COX-2) of NOS and COX. Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6-ketoprostaglandin F. ecNOS and COX-1, but not iNOS and COX-2, were upregulated in hyperoxia-injured lungs. The nitric oxide produced by ecNOS attenuated COX-1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. Although a high hydrogen ion concentration was unnecessary for excitation of COX-1, venule constriction in response to H+ was enhanced by COX-1 inhibition. Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalEuropean Respiratory Journal
Volume20
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Constitutive nitric oxide
  • Cyclo-oxygenase-1
  • Cyclo-oxygenase-2
  • Hypercapnic acidosis
  • Inducible nitric oxide synthase
  • Isocapnic acidosis
  • Synthase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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