Regulation of bovine endothelial constitutive nitric oxide synthase by oxygen

James K. Liao, Javier J. Zulueta, Feng Sheng Yu, Hai Bing Peng, Claudia G. Cote, Paul M. Hassoun

Research output: Contribution to journalArticlepeer-review

Abstract

Oxygen (O2) may regulate pulmonary vascular resistance through changes in endothelial nitric oxide (NO) production. To determine whether constitutive NO synthase (cNOS) is regulated by O2, we assessed cNOS expression and activity in bovine pulmonary artery endothelial cells exposed to different concentrations of O2. In a time-dependent manner, changes in O2 concentration from 95 to 3% produced a progressive decrease in cNOS mRNA and protein levels resulting in 4.8- and 4.3-fold reductions after 24 h, respectively. This correlated with changes in cNOS activity as determined by nitrite measurements. Compared with 20% O2, cNOS activity was increased 1.5- fold in 95% O2 and decreased 1.9-fold in 3% O2. A decrease in O2 concentration from 95 to 3% shortened cNOS mRNA half-life from 46 to 24 h and caused a 20-fold repression of cNOS gene transcription. Treatment with cycloheximide produced a threefold increase in cNOS mRNA at all O2 concentrations, suggesting that cNOS mRNA expression is negatively regulated under basal condition. We conclude that O2 upregulates cNOS expression through transcriptional and posttranscriptional mechanisms. A decrease in cNOS activity in the presence of low O2 levels, therefore, may contribute to hypoxia-induced vasoconstriction in the pulmonary circulation.

Original languageEnglish (US)
Pages (from-to)2661-2666
Number of pages6
JournalJournal of Clinical Investigation
Volume96
Issue number6
DOIs
StatePublished - Dec 1995

Keywords

  • gene regulation
  • hyperoxia
  • hypoxia
  • pulmonary

ASJC Scopus subject areas

  • Medicine(all)

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