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Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction.
Placenta. 2005 Feb-Mar; 26(2-3):242-50.P

Abstract

The vasoactive mediators nitric oxide and endothelin are both produced in and active in the uterine and placental vasculature. Inhibition of nitric oxide synthase (NOS) results in fetal growth restriction. Endothelin (ET-1) is upregulated in the setting of NOS inhibition. Our purpose was to determine the impact of ET-1 on uterine and placental perfusion in the pregnant rat treated with a NOS inhibitor. Timed-pregnant Sprague-Dawley rats were treated with L-NAME (2.5 mg/kg/h), with and without A-127722 (10 mg/kg/day), or their respective vehicles, for 1, 4, or 7 days beginning on day 14 of gestation. Blood flow to various organs was determined by microsphere infusion. Maternal and fetal plasma nitrate/nitrite (NOx) was determined by fluorometric assay. Uterine and placental perfusion was significantly decreased by NOS inhibition and was restored to normal by ETA antagonism at 1 and 4 days of infusion but not at 7 days. Maternal plasma NOx, but not fetal plasma NOx, was significantly decreased by NOS inhibition alone. ETA antagonism in combination with NOS inhibition significantly lowered fetal plasma NOx. These results indicate that ET-1 is an important regulator of uterine and placental perfusion in the NOS inhibition model of fetal growth restriction. Our results also suggest that maternal administration of L-NAME does not result in significant transport of L-NAME across the placenta, but that addition of an ETA antagonist results in increased placental perfusion, allowing L-NAME greater access to the fetal compartment.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. l-thaete@northwestern.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15708126

Citation

Thaete, L G., et al. "Endothelin and the Regulation of Uteroplacental Perfusion in Nitric Oxide Synthase Inhibition-induced Fetal Growth Restriction." Placenta, vol. 26, no. 2-3, 2005, pp. 242-50.
Thaete LG, Kushner DM, Dewey ER, et al. Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. Placenta. 2005;26(2-3):242-50.
Thaete, L. G., Kushner, D. M., Dewey, E. R., & Neerhof, M. G. (2005). Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. Placenta, 26(2-3), 242-50.
Thaete LG, et al. Endothelin and the Regulation of Uteroplacental Perfusion in Nitric Oxide Synthase Inhibition-induced Fetal Growth Restriction. Placenta. 2005 Feb-Mar;26(2-3):242-50. PubMed PMID: 15708126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. AU - Thaete,L G, AU - Kushner,D M, AU - Dewey,E R, AU - Neerhof,M G, PY - 2004/06/10/accepted PY - 2005/2/15/pubmed PY - 2005/7/6/medline PY - 2005/2/15/entrez SP - 242 EP - 50 JF - Placenta JO - Placenta VL - 26 IS - 2-3 N2 - The vasoactive mediators nitric oxide and endothelin are both produced in and active in the uterine and placental vasculature. Inhibition of nitric oxide synthase (NOS) results in fetal growth restriction. Endothelin (ET-1) is upregulated in the setting of NOS inhibition. Our purpose was to determine the impact of ET-1 on uterine and placental perfusion in the pregnant rat treated with a NOS inhibitor. Timed-pregnant Sprague-Dawley rats were treated with L-NAME (2.5 mg/kg/h), with and without A-127722 (10 mg/kg/day), or their respective vehicles, for 1, 4, or 7 days beginning on day 14 of gestation. Blood flow to various organs was determined by microsphere infusion. Maternal and fetal plasma nitrate/nitrite (NOx) was determined by fluorometric assay. Uterine and placental perfusion was significantly decreased by NOS inhibition and was restored to normal by ETA antagonism at 1 and 4 days of infusion but not at 7 days. Maternal plasma NOx, but not fetal plasma NOx, was significantly decreased by NOS inhibition alone. ETA antagonism in combination with NOS inhibition significantly lowered fetal plasma NOx. These results indicate that ET-1 is an important regulator of uterine and placental perfusion in the NOS inhibition model of fetal growth restriction. Our results also suggest that maternal administration of L-NAME does not result in significant transport of L-NAME across the placenta, but that addition of an ETA antagonist results in increased placental perfusion, allowing L-NAME greater access to the fetal compartment. SN - 0143-4004 UR - https://www.unboundmedicine.com/medline/citation/15708126/Endothelin_and_the_regulation_of_uteroplacental_perfusion_in_nitric_oxide_synthase_inhibition_induced_fetal_growth_restriction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143400404001614 DB - PRIME DP - Unbound Medicine ER -