Thaete L G, Neerhof M G, Silver R K
Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Northwestern University Medical School, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, USA.
J Soc Gynecol Investig. 2001 Jan-Feb;8(1):18-23.
To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition.
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.
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.
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.
确定内皮素（ET）在长期抑制一氧化氮合酶（NOS）的大鼠和未抑制NOS的大鼠的胎儿及胎盘生长中的作用。
将怀孕大鼠用N（ω）-硝基-L-精氨酸甲酯（L-NAME）或生理盐水处理，并分别给予三种ET受体拮抗剂之一或赋形剂。拮抗剂包括A-182086（非选择性）以及A-127722和FR-139317（均为ET(A)选择性）。在妊娠第14天开始治疗。在妊娠第21天，进行子宫切开术。记录产仔数，并测定存活率以及胎儿和胎盘重量。结果通过方差分析或Kruskal-Wallis非参数分析进行分析。
在未使用L-NAME的情况下，ET(A)选择性拮抗作用不影响胎儿和胎盘重量，但非选择性受体拮抗作用会使其显著降低（胎儿和胎盘重量分别为P<.001和P<.05）。输注L-NAME导致胎儿和胎盘生长受限（P<.001）。在输注L-NAME的情况下，与仅用L-NAME处理的动物相比，ET(A)选择性拮抗剂可增加胎儿和胎盘重量（P<.01），而非选择性拮抗剂则无此作用。L-NAME处理导致更多胎儿死亡（P<.05），但其发生率不受任何ET受体拮抗剂的显著影响。
单独的ET(A)拮抗作用不影响胎儿或胎盘生长，而ET(A)加ET(B)联合拮抗作用则导致胎儿和胎盘生长受限。在长期抑制NOS的情况下，ET(A)选择性拮抗作用可改善胎儿和胎盘生长，而ET(A)和ET(B)受体的拮抗作用则不能。内皮素通过ET(A)受体导致NOS抑制引起的生长受限。
