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

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

Research output: Contribution to journalArticle

80 Citations (Scopus)

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

Fingerprint

Nitric Oxide Synthase Type III
Ventilation
Gene Expression
Lung
Messenger RNA
Vascular Resistance
Proteins
Parturition
Pulmonary Ventilation
Ribonucleases
Vasodilation
In Situ Hybridization
Blood Vessels
Sheep
Nitric Oxide
Endothelial Cells
Gases
Western Blotting
RNA
Oxygen

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs. / Black, Stephen Matthew; Johengen, Michael J.; Ma, Zhi Dong; Bristow, James; Soifer, Scott J.

In: Journal of Clinical Investigation, Vol. 100, No. 6, 15.09.1997, p. 1448-1458.

Research output: Contribution to journalArticle

Black, Stephen Matthew ; Johengen, Michael J. ; Ma, Zhi Dong ; Bristow, James ; Soifer, Scott J. / Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 6. pp. 1448-1458.
@article{e108d3c43412471d8bb4eff0fdbc5080,
title = "Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs",
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.",
keywords = "Development, Endothelial cells, Endothelial nitric oxide synthase, Nitric oxide, Pulmonary circulation",
author = "Black, {Stephen Matthew} and Johengen, {Michael J.} and Ma, {Zhi Dong} and James Bristow and Soifer, {Scott J.}",
year = "1997",
month = "9",
day = "15",
doi = "10.1172/JCI119665",
language = "English (US)",
volume = "100",
pages = "1448--1458",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs

AU - Black, Stephen Matthew

AU - Johengen, Michael J.

AU - Ma, Zhi Dong

AU - Bristow, James

AU - Soifer, Scott J.

PY - 1997/9/15

Y1 - 1997/9/15

N2 - 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.

AB - 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.

KW - Development

KW - Endothelial cells

KW - Endothelial nitric oxide synthase

KW - Nitric oxide

KW - Pulmonary circulation

UR - http://www.scopus.com/inward/record.url?scp=0030875453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030875453&partnerID=8YFLogxK

U2 - 10.1172/JCI119665

DO - 10.1172/JCI119665

M3 - Article

VL - 100

SP - 1448

EP - 1458

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -