John Paul Zulueta - Academia.edu (original) (raw)
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Papers by John Paul Zulueta
Journal of Clinical Investigation, 1995
Oxygen (02) may regulate pulmonary vascular resistance through changes in endothelial nitric oxid... more Oxygen (02) may regulate pulmonary vascular resistance through changes in endothelial nitric oxide (NO) production. To determine whether constitutive NO synthase (cNOS) is regulated by 02, we assessed cNOS expression and activity in bovine pulmonary artery endothelial cells exposed to different concentrations of 02-In a time-dependent manner, changes in 02 concentration from 95 to 3% produced a progressive decrease in cNOS mRNA and protein levels resulting in 4.8and 43-fold reductions after 24 h, respectively. This correlated with changes in cNOS activity as determined by nitrite measurements. Compared with 20% 02, cNOS activity was increased 1.5-fold in 95% 02 and decreased 1.9-fold in 3% 02. A decrease in 02 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 02 concentrations, suggesting that cNOS mRNA expression is negatively regulated under basal condition. We conclude that 02 upregulates cNOS expression through transcriptional and posttranscriptional mechanisms. A decrease in cNOS activity in the presence of low 02 levels, therefore, may contribute to hypoxia-induced vasoconstriction in the pulmonary circulation. (J. Clin. Invest. 1995Invest. . 96:2661Invest. -2666
Journal of Clinical Investigation, 1995
Oxygen (02) may regulate pulmonary vascular resistance through changes in endothelial nitric oxid... more Oxygen (02) may regulate pulmonary vascular resistance through changes in endothelial nitric oxide (NO) production. To determine whether constitutive NO synthase (cNOS) is regulated by 02, we assessed cNOS expression and activity in bovine pulmonary artery endothelial cells exposed to different concentrations of 02-In a time-dependent manner, changes in 02 concentration from 95 to 3% produced a progressive decrease in cNOS mRNA and protein levels resulting in 4.8and 43-fold reductions after 24 h, respectively. This correlated with changes in cNOS activity as determined by nitrite measurements. Compared with 20% 02, cNOS activity was increased 1.5-fold in 95% 02 and decreased 1.9-fold in 3% 02. A decrease in 02 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 02 concentrations, suggesting that cNOS mRNA expression is negatively regulated under basal condition. We conclude that 02 upregulates cNOS expression through transcriptional and posttranscriptional mechanisms. A decrease in cNOS activity in the presence of low 02 levels, therefore, may contribute to hypoxia-induced vasoconstriction in the pulmonary circulation. (J. Clin. Invest. 1995Invest. . 96:2661Invest. -2666