Togashi H, Takizawa T, Kawahata M, Yamamoto M, Arishima K, Masaoka T
Department of Anatomy II, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
J Vet Med Sci. 1998 Aug;60(8):989-91. doi: 10.1292/jvms.60.989.
This work was conducted to determine whether the angiotensin-converting enzyme inhibitors (ACEIs) (enalapril and captopril) administered to mother rats prenatally can potentiate a re-opening of the neonatal ductus arteriosus (DA) induced by prostaglandin E2 (PGE2) after postnatal closure. A subcutaneous injection of PGE2 (4 micrograms) was administered to newborn rats 3 hr after a Cesarean delivery from females which had been orally given 0.1, 1 or 10 mg/kg/day of enalapril or 15 or 150 mg/kg/day of captopril from day 14 to day 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in the newborn rats of mothers who were transplacentally administered these agents compared to the controls, except at the low dose (0.1 mg/kg) group of enalapril. We found that the level in the neonatal lungs of 15-hydroxy prostaglandin dehydrogenase, a key enzyme that catalyzes PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected after maternal treatment with enalapril or captopril. These results indicate that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal ACEI treatment, but the catabolism of PGE2 in the lungs did not contribute to this response.
本研究旨在确定产前给母鼠施用血管紧张素转换酶抑制剂（ACEI）（依那普利和卡托普利）是否能增强产后闭合后由前列腺素E2（PGE2）诱导的新生大鼠动脉导管（DA）重新开放。从妊娠第14天到第20天，对雌性大鼠口服给予0.1、1或10mg/kg/天的依那普利或15或150mg/kg/天的卡托普利，剖宫产分娩后3小时，给新生大鼠皮下注射PGE2（4微克）。注射后每隔一段时间测定DA与肺动脉（PA）的比值。与对照组相比，经胎盘给予这些药物的母鼠的新生大鼠的DA/PA比值显著更高，但依那普利低剂量（0.1mg/kg）组除外。我们发现，用依那普利或卡托普利对母鼠进行处理后，15-羟基前列腺素脱氢酶（一种催化PGE2转化为其无活性代谢物15-酮-PGE2的关键酶）在新生大鼠肺中的水平不受影响。这些结果表明，母鼠接受ACEI治疗后，新生大鼠导管对PGE2的反应性增加是一种常见反应，但肺中PGE2的分解代谢对这种反应没有作用。
