Estrogen acutely stimulates nitric oxide synthase activity in fetal pulmonary artery endothelium

Regina L. Lantin-Hermoso, Charles R. Rosenfeld, Ivan S. Yuhanna, Zohre German, Zhong Chen, Philip W. Shaul

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Estrogen (E) has nitric oxide (NO)-mediated effects in certain vascular beds, and fetal E levels rise acutely with parturition, suggesting that E may be involved in NO-mediated pulmonary vasodilation at birth. We tested the hypothesis that E acutely stimulates NO synthase (NOS) activity in ovine fetal pulmonary artery endothelial cells (PAEC) by measuring L-[3H]arginine conversion to L-[3H]citrulline in intact cells. NOS activity in the presence of 17β-estradiol (E2β) rose in a dose-dependent manner, increasing 70- 100%, with a threshold concentration of 10-10 M. This effect was detectable within 5 min of E2β exposure, and the maximal response was comparable to that obtained with acetylcholine, which had a threshold concentration of 10-8 M. Ca2+ removal completely inhibited E2β- stimulated NOS activity, and activity with E2β and the Ca2+ ionophore A- 23187 was not additive: In addition, the expression of the endothelial isoform of NOS (eNOS) was not altered, and the inducible and neuronal NOS isoforms were not detected by immunoblot analysis. These findings indicate that E2β acutely stimulates eNOS by Ca2+ influx. Furthermore, E2β- stimulated NOS activity was fully inhibited by the E receptor (ER) antagonists tamoxifen and ICI-182,780, and ER mRNA expression was evident in reverse transcription-polymerase chain reaction assays. Thus E acutely stimulates eNOS activity in fetal PAEC via the activation of endothelial ER and increases in intracellular Ca2+.

Original languageEnglish (US)
Pages (from-to)L119-L126
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 17-1
StatePublished - Jul 1997


  • Calcium
  • Estrogen receptor
  • ICI-182,780
  • Tamoxifen
  • Transitional circulation

ASJC Scopus subject areas

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


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