Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats
Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats
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DOI：
10.1016/s1071-5576(00)00119-2
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Silver, RK
中科院分区：
文献类型：
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作者：
Thaete, LG;Neerhof, MG;Silver, RK
目的：探讨长期一氧化氮合酶(NOS)抑制对大鼠胎儿和胎盘生长发育的影响。方法：用N-奥米伽-硝基-L-精氨酸甲酯(L-NAME)或生理盐水处理妊娠大鼠，同时用3种ET受体拮抗剂或赋形剂中的一种进行干预。拮抗剂包括A-182086(非选择性)、A-127722和FR-139317(均为ETa选择性)。治疗开始于妊娠第14天。妊娠第21天，行子宫切开术。记录每窝产仔数，并测定存活率、胎儿和胎盘重量。结果采用方差分析或Kruskal-Wallis非参数分析。结果：在没有L名字的情况下，胎儿和胎盘的体重不受ETa选择性拮抗剂的影响，但可被非选择性受体拮抗剂显著降低(胎儿和胎盘的体重分别为P<；.001和P<；.05)。输注L-NAME导致胎儿和胎盘生长受限(P<；.001)。在L-NAME输液的环境中，与单独使用L-NAME的动物相比，ETa选择性拮抗剂(P<；.01)增加了胎儿和胎盘的体重，但非选择性拮抗剂没有增加胎儿和胎盘重量。使用L-NAME治疗的胎儿死亡较多(P<；0.05)，但ET受体拮抗剂中的任何一种都不显著影响胎儿和胎盘的发生。结论：单独使用内皮素-A拮抗剂不影响胎儿或胎盘的生长，而ETA和ETB拮抗剂联合使用则会导致胎儿和胎盘生长受限。在长期抑制一氧化氮合酶的情况下，ETA选择性拮抗剂可促进胎儿和胎盘的生长，而ETA和ETB受体拮抗剂均不能。内皮素通过ETA受体参与一氧化氮合酶抑制引起的生长抑制。版权所有(C)2001，由妇科调查学会提供。
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 (no-selective) as well as A-127722 and FR-139317 (both ETA 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 ETA-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 ETA-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 ETA plus ETB antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ETA-selective antagonism improved fetal and placental growth, whereas antagonism of both ETA and ETB receptor did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ETA receptor. Copyright (C) 2001 by the Society for Gynecologic Investigation.