Oxygen upregulates nitric oxide synthase gene expression in ovine fetal pulmonary artery endothelial cells.
Nitric oxide (NO) is critically involved in oxygen-mediated pulmonary vasodilatation in the fetus and newborn. We determined the effects of prolonged alterations in oxygenation on endothelial NO synthase (eNOS) gene expression in early passage ovine fetal intrapulmonary artery endothelial cells (PAEC). PAEC were exposed to PO2 = 50 or 150 mmHg for 48 h, and eNOS protein expression was evaluated by immunoblot analysis. eNOS protein expression was 2.7-fold greater at higher oxygen tension; eNOS upregulation was also evident after 24 h. Inducible NOS protein was not detectable by immunoblot at either level of oxygenation. In the lung, the effect of oxygen on eNOS expression may be specific to the endothelium, as eNOS expression in bronchiolar epithelial cells of Clara cell lineage was not altered by varying oxygen tension. The oxygen-related increase in eNOS protein in the fetal PAEC was associated with 2.5-fold greater NOS enzymatic activity. In parallel, there was a 2.8-fold rise in eNOS mRNA abundance. Thus eNOS gene expression in ovine fetal PAEC is upregulated by oxygen, and this is mediated at the level of gene transcription or mRNA stability. This process may play an important role in oxygen modulation of pulmonary vasomotor tone in the fetus and newborn.
North
A J
AJ
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Lau
K S
KS
Brannon
T S
TS
Wu
L C
LC
Wells
L B
LB
German
Z
Z
Shaul
P W
PW
D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005333:Fetus / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D010100:Oxygen