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Influence of ET(B) receptor antagonism on pregnancy outcome in rats.
J Soc Gynecol Investig. 2001 Jul-Aug; 8(4):239-44.JS

Abstract

OBJECTIVE

To determine the effect of endothelin-B (ET(B))-selective receptor antagonism on pregnancy outcome in normal rats.

METHODS

ET(B) receptor antagonist (A-192621; 5.0, 10.0, and 15.0 mg/kg per day) or vehicle was infused subcutaneously for 7 days by osmotic pump. Infusion was begun on day 14 of a 22-day gestation. Nonpregnant animals were treated similarly, and blood pressure (BP) responses and plasma antagonist levels were compared to those in pregnant animals. Mean arterial pressure (MAP) was measured on days 1, 4, and 7 of the infusion. Plasma ET(B) antagonist levels were measured on day 7 of infusion. On gestational day 21, fetal and placental weights and viability were evaluated at hysterotomy. Data were analyzed by analysis of variance and are presented as mean +/- standard error of the mean.

RESULTS

Fetal and placental weights were significantly lower at doses of 10 and 15 mg/kg per day of the ET(B) antagonist compared with vehicle-treated controls (P <.001); these effects were less severe at 15 than at 10 mg/kg per day despite a fourfold higher plasma level of antagonist. Mean arterial pressure was significantly higher at 10 and 15 mg/kg per day compared with controls, but only on infusion day 1 (P <.05). In contrast, MAPs for nonpregnant rats were elevated throughout the infusion at all doses of the ET(B) antagonist (P <.05).

CONCLUSIONS

ET(B) receptor antagonism inhibited fetal growth and increased maternal MAP in a dose-dependent manner, although the effect on BP was not sustained in pregnant animals. ET(B) receptor antagonism is detrimental to pregnancy outcome in the rat.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

11525900

Citation

Madsen, K M., et al. "Influence of ET(B) Receptor Antagonism On Pregnancy Outcome in Rats." Journal of the Society for Gynecologic Investigation, vol. 8, no. 4, 2001, pp. 239-44.
Madsen KM, Neerhof MG, Wessale JL, et al. Influence of ET(B) receptor antagonism on pregnancy outcome in rats. J Soc Gynecol Investig. 2001;8(4):239-44.
Madsen, K. M., Neerhof, M. G., Wessale, J. L., & Thaete, L. G. (2001). Influence of ET(B) receptor antagonism on pregnancy outcome in rats. Journal of the Society for Gynecologic Investigation, 8(4), 239-44.
Madsen KM, et al. Influence of ET(B) Receptor Antagonism On Pregnancy Outcome in Rats. J Soc Gynecol Investig. 2001 Jul-Aug;8(4):239-44. PubMed PMID: 11525900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of ET(B) receptor antagonism on pregnancy outcome in rats. AU - Madsen,K M, AU - Neerhof,M G, AU - Wessale,J L, AU - Thaete,L G, PY - 2001/8/30/pubmed PY - 2001/10/26/medline PY - 2001/8/30/entrez SP - 239 EP - 44 JF - Journal of the Society for Gynecologic Investigation JO - J Soc Gynecol Investig VL - 8 IS - 4 N2 - OBJECTIVE: To determine the effect of endothelin-B (ET(B))-selective receptor antagonism on pregnancy outcome in normal rats. METHODS: ET(B) receptor antagonist (A-192621; 5.0, 10.0, and 15.0 mg/kg per day) or vehicle was infused subcutaneously for 7 days by osmotic pump. Infusion was begun on day 14 of a 22-day gestation. Nonpregnant animals were treated similarly, and blood pressure (BP) responses and plasma antagonist levels were compared to those in pregnant animals. Mean arterial pressure (MAP) was measured on days 1, 4, and 7 of the infusion. Plasma ET(B) antagonist levels were measured on day 7 of infusion. On gestational day 21, fetal and placental weights and viability were evaluated at hysterotomy. Data were analyzed by analysis of variance and are presented as mean +/- standard error of the mean. RESULTS: Fetal and placental weights were significantly lower at doses of 10 and 15 mg/kg per day of the ET(B) antagonist compared with vehicle-treated controls (P <.001); these effects were less severe at 15 than at 10 mg/kg per day despite a fourfold higher plasma level of antagonist. Mean arterial pressure was significantly higher at 10 and 15 mg/kg per day compared with controls, but only on infusion day 1 (P <.05). In contrast, MAPs for nonpregnant rats were elevated throughout the infusion at all doses of the ET(B) antagonist (P <.05). CONCLUSIONS: ET(B) receptor antagonism inhibited fetal growth and increased maternal MAP in a dose-dependent manner, although the effect on BP was not sustained in pregnant animals. ET(B) receptor antagonism is detrimental to pregnancy outcome in the rat. SN - 1071-5576 UR - https://www.unboundmedicine.com/medline/citation/11525900/Influence_of_ET_B__receptor_antagonism_on_pregnancy_outcome_in_rats_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:11525900 DB - PRIME DP - Unbound Medicine ER -