Vieira-Filho Leucio D, Lucena-Júnior José M, Barreto Izabel S S, Angelim José L C, Paixão Ana D O
Department of Physiology and Pharmacology, Biological Science Center, Federal University of Pernambuco, Av. Prof. Moraes Rego, s/n, Cidade Universitaria, 50670-901 Recife, PE, Brazil.
Fundam Clin Pharmacol. 2008 Aug;22(4):379-86. doi: 10.1111/j.1472-8206.2008.00604.x.
Acetylsalicylic acid (ASA) during pregnancy reaches the fetus. It seems important to know possible repercussions of ASA on later renal function of the offspring, as well as repercussions of this drug on factors that may influence fetal development, such as maternal plasma volume and placental oxidative stress. It was evaluated whether ASA changes maternal plasma volume and/or placental oxidative stress, fetal weight and renal function of the offspring at adult life. ASA (100 mg/kg/day, p.o., dissolved in ETOH 10%) or ETOH 10% was administered to Wistar rat dams, from the day 7 to day 20 of pregnancy/parturition. Plasma volume and the placental oxidative stress were evaluated on day 20 of pregnancy, using, respectively, the Evans blue dye and the thiobarbituric acid reactive substances methods. Mean arterial pressure, renal blood flow (RBF) and glomerular filtration rate (GFR) were evaluated in the anesthetized offspring, at the age of 90 days, using a blood pressure transducer, a flow probe and inulin clearance respectively. Plasma volume was 76% (P < 0.05) higher in ASA compared with that in control dams, but placental oxidative stress was the same for both groups. Fetal body weight, the number of nephrons, GFR, RBF and renal vascular resistance were similar for the same gender among the offspring of the two groups. However, reduced hematocrit (9.8%, P < 0.05), increased renal plasma flow (27%, P < 0.05) and reduced filtration fraction (32%, P < 0.05) were seen in the female offspring. In conclusion, although ASA had increased maternal plasma volume, it did not change nephrogenesis nor GFR in the adult offspring. The changes in renal plasma flow and filtration fraction seen in the ASA female offspring might partially be due to the reduced hematocrit.
孕期服用的乙酰水杨酸(ASA)会进入胎儿体内。了解ASA对后代后期肾功能的潜在影响,以及该药物对可能影响胎儿发育的因素(如母体血容量和胎盘氧化应激)的影响似乎很重要。本研究评估了ASA是否会改变母体血容量和/或胎盘氧化应激、后代成年后的胎儿体重和肾功能。在妊娠/分娩的第7天至第20天,给Wistar大鼠母鼠灌胃给予ASA(100mg/kg/天,溶于10%乙醇)或10%乙醇。分别在妊娠第20天,使用伊文思蓝染料法和硫代巴比妥酸反应物质法评估母体血容量和胎盘氧化应激。在90日龄的麻醉后代中,分别使用血压传感器、血流探头和菊粉清除率评估平均动脉压、肾血流量(RBF)和肾小球滤过率(GFR)。与对照组母鼠相比,ASA组母鼠的血容量高76%(P<0.05),但两组的胎盘氧化应激相同。两组后代中,相同性别的胎儿体重、肾单位数量、GFR、RBF和肾血管阻力相似。然而,雌性后代的血细胞比容降低(9.8%,P<0.05),肾血浆流量增加(27%,P<0.05),滤过分数降低(32%,P<0.05)。总之,尽管ASA增加了母体血容量,但并未改变成年后代的肾发生和GFR。ASA雌性后代肾血浆流量和滤过分数的变化可能部分归因于血细胞比容的降低。