Vasodilator effects of dehydroepiandrosterone (DHEA) on fetal pulmonary circulation: An experimental study in pregnant sheep

Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in severa...

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Bibliographic Details
Published in:PloS one 2018-06, Vol.13 (6), p.e0198778
Main Authors: Sharma, Dyuti, Coridon, Hélène, Aubry, Estelle, Houeijeh, Ali, Houfflin-Debarge, Véronique, Besson, Rémi, Deruelle, Philippe, Storme, Laurent
Format: Article
Language:English
Subjects:
Animal models
Animals
Biology and Life Sciences
Blood
Blood circulation
Chronic obstructive pulmonary disease
Dehydroepiandrosterone
Dehydroepiandrosterone - pharmacology
Disease
Dose-Response Relationship, Drug
Female
Fetal development
Fetus - blood supply
Fetuses
Gases
Gestation
Gynecology
Health aspects
Hospitals
Hypertension
Intravenous administration
Intravenous infusion
Measurement
Medicine and Health Sciences
Morbidity
Neonates
Nitric oxide
Obstetrics
Ostomy
Ovis aries
Pediatrics
Pharmacology
Physical Sciences
Physiology
Pregnancy
Pulmonary arteries
Pulmonary circulation
Pulmonary Circulation - drug effects
Pulmonary hypertension
Sheep
Studies
Surgery
Testing
Time Factors
Uterus
Vasodilator Agents - pharmacology
Veins & arteries
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Summary:Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0198778