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. 2018 Jun 27;13(6):e0198778.
doi: 10.1371/journal.pone.0198778. eCollection 2018.

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

Dyuti Sharma  1   2 , Hélène Coridon  1   3 , Estelle Aubry  1   2 , Ali Houeijeh  1   4 , Véronique Houfflin-Debarge  1   5 , Rémi Besson  1   2 , Philippe Deruelle  1   5 , Laurent Storme  1   4
Affiliations

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

Dyuti Sharma et al. PLoS One. .

Abstract

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<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Change in fetal heart rate, FHR (A), pulmonary artery pressure, PAP (B), left pulmonary artery blood flow, LPA flow (C) and pulmonary vascular resistance, PVR (D) in response to bolus of 6 mg DHEA compared to bolus of control solution 2%.
Values are means ±SEMs, n = 5, (DHEA 6 mg) and n = 5, (control 2%).
Fig 2
Fig 2. Change in fetal heart rate, FHR (A), pulmonary artery pressure, PAP (B), left pulmonary artery blood flow, LPA flow (C) and pulmonary vascular resistance, PVR (D) in response to bolus of 12 mg DHEA compared to bolus of control solution 2%.
Values are means ±SEMs, n = 5, (DHEA 12 mg) and n = 5, (control 2%). *p<0.05 significant difference of FHR comparing baseline vs. 12 mg DHEA bolus and ***p<0.001 comparing baseline vs. 12 mg- DHEA bolus (one-way ANOVA) and comparing 12 mg- DHEA bolus vs. control 2% (Two-way ANOVA).
Fig 3
Fig 3. Change in fetal heart rate, FHR (A), pulmonary artery pressure, PAP (B), left pulmonary artery blood flow, LPA flow (C) and pulmonary vascular resistance, PVR (D) in response to bolus of 24 mg DHEA compared to bolus of control solution 4%.
Values are means ±SEMs, n = 5, (DHEA 24 mg) and n = 4, (control 4%). *p<0.05 significant difference of FHR comparing baseline vs. 24 mg DHEA bolus ***p<0.001 comparing baseline vs. 24 mg- DHEA bolus (one-way ANOVA) and comparing 24 mg- DHEA bolus vs. control 4% (Two-way ANOVA).
Fig 4
Fig 4. Groups-related changes in PVR with increasing doses of DHEA bolus infusion.
Maximum percentage of variation of PVR with increasing doses of DHEA bolus infusion with significant difference in 24 mg DHEA group compared to 6 mg DHEA and to 12 mg DHEA groups (Two-way ANOVA).
Fig 5
Fig 5. Time-related changes in PVR before and 15 min after DHEA bolus infusion, 30 min after 30 mg LNA bolus infusion.
(A) comparison of PVR between 30 mg LNA infusion (n = 5), DHEA 12 mg infusion (n = 5) and LNA+DHEA 12 mg infusion (n = 5); (B) maximum percentage of PVR with 30 mg LNA, or DHEA 12 mg bolus infusion with and without 30 mg LNA pre-treatment; (C) comparison of PVR between 30 mg LNA infusion (n = 5), DHEA 24 mg infusion(n = 5) and LNA+DHEA 24 mg infusion (n = 4); (D) maximum percentage of PVR with 30 mg LNA, or DHEA 24 mg bolus infusion with and without 30 mg LNA pre-treatment.
See this image and copyright information in PMC

References

    1. Tuder RM, Stacher E, Robinson J, Kumar R, Graham BB. Pathology of Pulmonary Hypertension. Clinics in Chest Medicine. 2013. December;34(4):639–50. doi: 10.1016/j.ccm.2013.08.009 - DOI - PubMed
    1. Cassin S, Dawes GS, Ross BB. Pulmonary blood flow and vascular resistance in immature fetal lambs. J Physiol (Lond). 1964. May;171:80–9. - PMC - PubMed
    1. Velvis H, Moore P, Heymann MA. Prostaglandin Inhibition Prevents the Fall in Pulmonary Vascular Resistance as a Result of Rhythmic Distension of the Lungs in Fetal Lambs. Pediatric Research. 1991. July;30(1):62–8. doi: 10.1203/00006450-199107000-00013 - DOI - PubMed
    1. Ziegler JW, Ivy DD, Fox JJ, Kinsella JP, Clarke WR, Abman SH. Dipyridamole, a cGMP phosphodiesterase inhibitor, causes pulmonary vasodilation in the ovine fetus. American Journal of Physiology-Heart and Circulatory Physiology. 1995. August;269(2):H473–9. - PubMed
    1. Assali NS, Kirschbaum TH Dilts PV J. Effects of hyperbaric oxygen on uteroplacental and fetal circulation. Circ Res. 1968. May;22(5):573–88. - PubMed