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Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy.
Life Sci. 2012 Oct 15; 91(13-14):583-6.LS

Abstract

AIMS

Endothelin receptor A (ET(A)) antagonism normalizes fetal growth in several models of rodent fetal growth restriction (FGR). Our aims were to determine the levels of ET(A) antagonist in maternal and fetal plasma following chronic maternal administration, and to determine its impact on pregnancy outcome, survival and growth of rat pups.

MAIN METHODS

Timed pregnant rats were treated with one of two endothelin receptor antagonists or vehicle, from gestation day 14-21 (term=22 days). The antagonists and their respective doses were ABT-546 (20mg/kg/day) and FR139317 (12 mg/kg/day). On day 21, in six rats per group, maternal and fetal plasma ABT-546 was assayed by HPLC. Five additional rats in each group delivered spontaneously and nursed their pups through postpartum day 7. Viability of newborns, oxygen saturation, litter sizes, and pup weights were recorded on postpartum days 1 and 7.

KEY FINDINGS

Fetal antagonist levels reached only 2% of maternal levels (p<0.01). There were no significant differences among groups in length of gestation; litter size; survival, number and weight of live pups at birth and at 7 days postpartum; and tissue oxygen saturation.

SIGNIFICANCE

Maternal administration of an ET(A) antagonist, at a dose sufficient to ameliorate FGR, has no adverse impact on survival and growth of neonatal rat pups. ET(A) antagonism, delivered maternally, produces sufficiently low fetal plasma levels of antagonist so as not to present a survival threat to the neonatal pups. The beneficial effects of maternally administered ET(A) antagonism on fetal growth occur in the maternal, not the fetal, compartment.

Authors+Show Affiliations

Department of Obstetrics & Gynecology, Evanston Northwestern Healthcare, Evanston, IL, USA. Lthaete@northshore.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

22406077

Citation

Thaete, Larry G., et al. "Endothelin Receptor Antagonist Has Limited Access to the Fetal Compartment During Chronic Maternal Administration Late in Pregnancy." Life Sciences, vol. 91, no. 13-14, 2012, pp. 583-6.
Thaete LG, Khan S, Synowiec S, et al. Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy. Life Sci. 2012;91(13-14):583-6.
Thaete, L. G., Khan, S., Synowiec, S., Dayton, B. D., Bauch, J., & Neerhof, M. G. (2012). Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy. Life Sciences, 91(13-14), 583-6. https://doi.org/10.1016/j.lfs.2012.02.018
Thaete LG, et al. Endothelin Receptor Antagonist Has Limited Access to the Fetal Compartment During Chronic Maternal Administration Late in Pregnancy. Life Sci. 2012 Oct 15;91(13-14):583-6. PubMed PMID: 22406077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy. AU - Thaete,Larry G, AU - Khan,Saira, AU - Synowiec,Sylvia, AU - Dayton,Brian D, AU - Bauch,Joy, AU - Neerhof,Mark G, Y1 - 2012/03/03/ PY - 2011/11/02/received PY - 2012/01/19/revised PY - 2012/02/13/accepted PY - 2012/3/13/entrez PY - 2012/3/13/pubmed PY - 2013/1/8/medline SP - 583 EP - 6 JF - Life sciences JO - Life Sci VL - 91 IS - 13-14 N2 - AIMS: Endothelin receptor A (ET(A)) antagonism normalizes fetal growth in several models of rodent fetal growth restriction (FGR). Our aims were to determine the levels of ET(A) antagonist in maternal and fetal plasma following chronic maternal administration, and to determine its impact on pregnancy outcome, survival and growth of rat pups. MAIN METHODS: Timed pregnant rats were treated with one of two endothelin receptor antagonists or vehicle, from gestation day 14-21 (term=22 days). The antagonists and their respective doses were ABT-546 (20mg/kg/day) and FR139317 (12 mg/kg/day). On day 21, in six rats per group, maternal and fetal plasma ABT-546 was assayed by HPLC. Five additional rats in each group delivered spontaneously and nursed their pups through postpartum day 7. Viability of newborns, oxygen saturation, litter sizes, and pup weights were recorded on postpartum days 1 and 7. KEY FINDINGS: Fetal antagonist levels reached only 2% of maternal levels (p<0.01). There were no significant differences among groups in length of gestation; litter size; survival, number and weight of live pups at birth and at 7 days postpartum; and tissue oxygen saturation. SIGNIFICANCE: Maternal administration of an ET(A) antagonist, at a dose sufficient to ameliorate FGR, has no adverse impact on survival and growth of neonatal rat pups. ET(A) antagonism, delivered maternally, produces sufficiently low fetal plasma levels of antagonist so as not to present a survival threat to the neonatal pups. The beneficial effects of maternally administered ET(A) antagonism on fetal growth occur in the maternal, not the fetal, compartment. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/22406077/Endothelin_receptor_antagonist_has_limited_access_to_the_fetal_compartment_during_chronic_maternal_administration_late_in_pregnancy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(12)00089-6 DB - PRIME DP - Unbound Medicine ER -