| Impact of endothelin A receptor antagonist selectivity in chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat. | |
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MedLine Citation:
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PMID: 20504166 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Endothelin receptor A (ETA) antagonism improves fetal and placental growth and placental perfusion on days 1 and 4, but not day 7 of a 7-day infusion of a nitric oxide synthase (NOS) inhibitor. Our purpose was to evaluate the significance of the degree of ETA antagonist selectivity on uteroplacental perfusion and fetal growth on day 7 of chronic NOS inhibition. METHODS: Timed-pregnant rats were treated with the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg/h) with and without one of the following ETA antagonists or their respective vehicles for 7 days beginning on day 14 of gestation: A-127722 (2,000-fold selective for ETA over ETB), FR139317 (8,000-fold ETA-selective), or ABT-546 (28,000-fold ETA-selective). Uterine and placental perfusion, as well as fetal and placental weight, was evaluated at the 7th day of treatment (gestation day 21). RESULTS: L-NAME administration resulted in a significant reduction in uterine and placental perfusion as well as fetal and placental growth. In the setting of NOS inhibition, ETA antagonism did not improve uterine or placental perfusion or fetal growth after 7 days of infusion irrespective of the degree of selectivity of the antagonist used. CONCLUSIONS: ETA antagonism, irrespective of the degree of receptor selectivity, does not improve fetal growth or uteroplacental perfusion on day 7 of chronic NOS inhibition. |
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Authors:
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Mark G Neerhof; Sylvia Synowiec; Saira Khan; Larry G Thaete |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Hypertension in pregnancy : official journal of the International Society for the Study of Hypertension in Pregnancy Volume: 29 ISSN: 1525-6065 ISO Abbreviation: Hypertens Pregnancy Publication Date: 2010 |
Date Detail:
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Created Date: 2010-08-09 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421297 Medline TA: Hypertens Pregnancy Country: England |
Other Details:
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Languages: eng Pagination: 284-93 Citation Subset: IM |
Affiliation:
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Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, North Shore University Health System, Evanston, Illinois 60201, USA. mneerhof@ enh.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Female Fetal Growth Retardation / chemically induced, metabolism* Male NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase / antagonists & inhibitors*, metabolism Pregnancy Rats Rats, Sprague-Dawley Receptors, Endothelin / antagonists & inhibitors*, metabolism Uterus / drug effects, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HD046968/HD/NICHD NIH HHS; R01 HD046968-05/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Endothelin; 50903-99-6/NG-Nitroarginine Methyl Ester; EC 1.14.13.39/Nitric Oxide Synthase |
| Comments/Corrections | |
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