Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs

Stephen M. Black, Michael J. Johengen, Zhi Dong Ma, James Bristow, Scott J. Soifer

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O2 ventilation increased PBF and decreased PVR more than rhythmic distension (P < 0.05). Rhythmic distension increased eNOS mRNA expression; O2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression (P < 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O2 or to shear stress. 95% O2 increased eNOS mRNA and protein expression (P < 0.05). Shear stress increased eNOS mRNA and protein expression (P < 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth.

Original languageEnglish (US)
Pages (from-to)1448-1458
Number of pages11
JournalJournal of Clinical Investigation
Volume100
Issue number6
DOIs
StatePublished - Sep 15 1997

Keywords

  • Development
  • Endothelial cells
  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Pulmonary circulation

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs'. Together they form a unique fingerprint.

  • Cite this