Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs
by
Dyuti Sharma 1,2, Estelle Aubry 1,2, Thavarak Ouk 3, Ali Houeijeh 1,4, Véronique Houfflin-Debarge 1,5, Rémi Besson 1,2, Philippe Deruelle 1,5 and Laurent Storme 1,4,*
Dyuti Sharma 1,2, Estelle Aubry 1,2, Thavarak Ouk 3, Ali Houeijeh 1,4, Véronique Houfflin-Debarge 1,5, Rémi Besson 1,2, Philippe Deruelle 1,5 and Laurent Storme 1,4,*
1
University Lille, CHU Lille, EA 4489, Perinatal Environment and Health, F-59000 Lille, France
2
CHU Lille, Department of Paediatric Surgery, F-59000 Lille, France
3
University Lille, Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, F-59000 Lille, France
4
CHU Lille, Department of Neonatology, F-59000 Lille, France
5
CHU Lille, Department of Obstetrics and Gynecology, F-59000 Lille, France
*
Author to whom correspondence should be addressed.
Nutrients 2017, 9(7), 761; https://doi.org/10.3390/nu9070761
Received: 23 May 2017 / Revised: 7 July 2017 / Accepted: 10 July 2017 / Published: 16 July 2017
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.
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Keywords:
polyunsaturated fatty acids; diet; persistent pulmonary hypertension of the newborn; prematurity; fetal pulmonary circulation
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MDPI and ACS Style
Sharma, D.; Aubry, E.; Ouk, T.; Houeijeh, A.; Houfflin-Debarge, V.; Besson, R.; Deruelle, P.; Storme, L. Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs. Nutrients 2017, 9, 761.
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