Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation
The Pediatric Heart Lung Center, Departments of 1 Pediatrics and 2 Internal Medicine, University of Colorado School of Medicine, Denver, Colorado 80262; and 3 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75235 Prolonged infusions of 17 -estradiol reduce...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 281; no. 3; pp. H1005 - H1014 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.09.2001
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Subjects | |
Online Access | Get full text |
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Summary: | The Pediatric Heart Lung Center, Departments of 1 Pediatrics
and 2 Internal Medicine, University of Colorado School of
Medicine, Denver, Colorado 80262; and 3 Department of
Pediatrics, University of Texas Southwestern Medical Center,
Dallas, Texas 75235
Prolonged infusions of 17 -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 (F I O 2 ). 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 F I O 2
[change in PVR 30 ± 6% (CTRL) vs. +10 ± 13%, (ICI),
P < 0.05] without reducing the vasodilator response
to ventilation with high F I O 2 [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.
prostacyclin; prostacyclin synthase; cyclooxygenase; newborn |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.2001.281.3.h1005 |