Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension

Philip W. Shaul, Ivan S. Yuhanna, Zohre German, Zhong Chen, Robin H Steinhorn, Frederick C. Morin

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically involved in the cardiopulmonary transition from fetal to neonatal life. We have previously shown that NO-dependent relaxation is attenuated in intrapulmonary arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal ligation of the ductus arteriosus. In the present study, we determined whether this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS) protein expression were assessed in lungs from near- term control lambs and PHT lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS enzymatic activity was also diminished in PHT vs. control lung (60 ± 3 vs. 110 ± 7 fmol · mg protein- 1 · min-1, respectively). Paralleling the declines in eNOS protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle growth, diminished eNOS expression may contribute to both the abnormal vasoreactivity and the excessive muscularization of the pulmonary circulation in fetal PHT.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume272
Issue number5 16-5
StatePublished - May 1997
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Pulmonary Hypertension
Gene Expression
Lung
Nitric Oxide
Proteins
Nitric Oxide Synthase
Ligation
Ductus Arteriosus
Pulmonary Circulation
Vascular Smooth Muscle
Vasodilation
Arteries
Messenger RNA
Growth

Keywords

  • Ductus arteriosus
  • Immunoblotting
  • Nitric oxide
  • Persistent fetal circulation syndrome
  • Polymerase chain reaction
  • Pulmonary circulation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. / Shaul, Philip W.; Yuhanna, Ivan S.; German, Zohre; Chen, Zhong; Steinhorn, Robin H; Morin, Frederick C.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 272, No. 5 16-5, 05.1997.

Research output: Contribution to journalArticle

Shaul, Philip W. ; Yuhanna, Ivan S. ; German, Zohre ; Chen, Zhong ; Steinhorn, Robin H ; Morin, Frederick C. / Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997 ; Vol. 272, No. 5 16-5.
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