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Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats.
J Soc Gynecol Investig. 2001 Jan-Feb; 8(1):18-23.JS

Abstract

OBJECTIVE

To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition.

METHODS

Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317 (both ET(A) selective). Treatment was begun on day 14 of gestation. On gestational day 21, a hysterotomy was done. Litter size was recorded, and viability and fetal and placental weights were determined. Results were analyzed by analysis of variance or by a Kruskal-Wallis nonparametric analysis.

RESULTS

In the absence of L-NAME, fetal and placental weights were not affected by ET(A)-selective antagonism but were significantly decreased by nonselective receptor antagonism (P <.001 and P <.05 for fetal and placental weights, respectively). Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001). In the setting of L-NAME infusion, fetal and placental weights were increased by the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist, compared with weights from animals treated with L-NAME alone. There were more fetal deaths with L-NAME treatment (P <.05), but their occurrence was not significantly affected by any of the ET receptor antagonists.

CONCLUSIONS

Endothelin-A antagonism alone did not affect fetal or placental growth, whereas combined ET(A) plus ET(B) antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ET(A)-selective antagonism improved fetal and placental growth, whereas antagonism of both ET(A) and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ET(A) receptor.

Authors+Show Affiliations

Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Northwestern University Medical School, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11223352

Citation

Thaete, L G., et al. "Differential Effects of Endothelin a and B Receptor Antagonism On Fetal Growth in Normal and Nitric Oxide-deficient Rats." Journal of the Society for Gynecologic Investigation, vol. 8, no. 1, 2001, pp. 18-23.
Thaete LG, Neerhof MG, Silver RK. Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats. J Soc Gynecol Investig. 2001;8(1):18-23.
Thaete, L. G., Neerhof, M. G., & Silver, R. K. (2001). Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats. Journal of the Society for Gynecologic Investigation, 8(1), 18-23.
Thaete LG, Neerhof MG, Silver RK. Differential Effects of Endothelin a and B Receptor Antagonism On Fetal Growth in Normal and Nitric Oxide-deficient Rats. J Soc Gynecol Investig. 2001 Jan-Feb;8(1):18-23. PubMed PMID: 11223352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats. AU - Thaete,L G, AU - Neerhof,M G, AU - Silver,R K, PY - 2001/2/27/pubmed PY - 2001/5/18/medline PY - 2001/2/27/entrez SP - 18 EP - 23 JF - Journal of the Society for Gynecologic Investigation JO - J Soc Gynecol Investig VL - 8 IS - 1 N2 - OBJECTIVE: To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition. METHODS: Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317 (both ET(A) selective). Treatment was begun on day 14 of gestation. On gestational day 21, a hysterotomy was done. Litter size was recorded, and viability and fetal and placental weights were determined. Results were analyzed by analysis of variance or by a Kruskal-Wallis nonparametric analysis. RESULTS: In the absence of L-NAME, fetal and placental weights were not affected by ET(A)-selective antagonism but were significantly decreased by nonselective receptor antagonism (P <.001 and P <.05 for fetal and placental weights, respectively). Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001). In the setting of L-NAME infusion, fetal and placental weights were increased by the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist, compared with weights from animals treated with L-NAME alone. There were more fetal deaths with L-NAME treatment (P <.05), but their occurrence was not significantly affected by any of the ET receptor antagonists. CONCLUSIONS: Endothelin-A antagonism alone did not affect fetal or placental growth, whereas combined ET(A) plus ET(B) antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ET(A)-selective antagonism improved fetal and placental growth, whereas antagonism of both ET(A) and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ET(A) receptor. SN - 1071-5576 UR - https://www.unboundmedicine.com/medline/citation/11223352/Differential_effects_of_endothelin_A_and_B_receptor_antagonism_on_fetal_growth_in_normal_and_nitric_oxide_deficient_rats_ DB - PRIME DP - Unbound Medicine ER -