Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation

Thomas A. Parker, Sam Afshar, John P. Kinsella, Theresa R. Grover, Sarah Gebb, Mark Geraci, Philip W. Shaul, Chad M.T. Cryer, Steven H. Abman

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Prolonged infusions of 17β-estradiol reduce fetal pulmonary vascular resistance (PVR), but the effects of endogenous estrogens in the fetal pulmonary circulation are unknown. To test the hypothesis that endogenous estrogen promotes pulmonary vasodilation at birth, we studied the hemodynamic effects of prolonged estrogen-receptor blockade during late gestation and at birth in fetal lambs. We treated chronically prepared fetal lambs with ICI-182,780 (ICI, a specific estrogen-receptor blocker, n = 5) or 1% DMSO (CTRL, n = 5) for 7 days and then measured pulmonary hemodynamic responses to ventilation with low- and high-fraction inspired oxygen (FIO2). Treatment with ICI did not change basal fetal PVR or arterial blood gas tensions. However, treatment with ICI abolished the vasodilator response to ventilation with low FIO2 [change in PVR -30 ± 6% (CTRL) vs. +10 ± 13%, (ICI), P < 0.05] without reducing the vasodilator response to ventilation with high FIO2 [change in PVR, -73 ± 3% (CTRL) vs. -77 ± 4%, (ICI); P = not significant]. ICI treatment reduced prostacyclin synthase (PGIS) expression by 33% (P < 0.05) without altering expression of endothelial nitric oxide synthase or cyclooxygenase-1 and -2. In situ hybridization and immunohistochemistry revealed that PGIS is predominantly expressed in the airway epithelium of late gestation fetal lambs. We conclude that prolonged estrogen-receptor blockade inhibits the pulmonary vasodilator response at birth and that this effect may be mediated by downregulation of PGIS. We speculate that estrogen exposure during late gestation prepares the pulmonary circulation for postnatal adaptation.

Original languageEnglish (US)
Pages (from-to)H1005-H1014
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number3 50-3
StatePublished - Oct 1 2001

Keywords

  • Cyclooxygenase
  • Newborn
  • Prostacyclin
  • Prostacyclin synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Parker, T. A., Afshar, S., Kinsella, J. P., Grover, T. R., Gebb, S., Geraci, M., Shaul, P. W., Cryer, C. M. T., & Abman, S. H. (2001). Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation. American Journal of Physiology - Heart and Circulatory Physiology, 281(3 50-3), H1005-H1014.