The pathophysiological study of pregnancy induced hypertension in transgenic mice carrying both human renin and angiotensinogen genes

目的：本研究旨在通过将携带人血管紧张素原基因的转基因小鼠与携带人血管紧张素原基因的小鼠杂交，分析妊娠高血压综合征（PIH）的病理生理变化。材料与方法：采用尾套法测定妊娠早期、中期和晚期转基因小鼠和野生型对照小鼠的收缩压。取孕18 d的孕鼠的胎儿、胎盘、母肾、心脏和血液<th>，用放射免疫法测定其血浆中人（h）-肾素和血管紧张素（AT）Ⅱ的浓度。结果：转基因小鼠妊娠中期收缩压开始升高，分娩前1天收缩压达到较高水平，妊娠后期收缩压下降。妊娠期高血压在分娩后恢复至正常水平。转基因小鼠的肾脏和胎儿重量显著低于野生型小鼠，但心脏和胎盘重量无差异。口服喹那普利和坎地沙坦酯可改善妊高征模型小鼠的高血压和降低胎重。在转基因小鼠中，h-肾素仅在胎盘和母体血浆中检测到，且胎盘和血浆AT Ⅱ浓度均显著高于对照组。结论：本研究表明，转基因小鼠妊娠后期胎盘和血浆h-肾素和AT Ⅱ浓度的过度升高导致高血压。

Objectives : The aim of this study is to analyze pathophysiological changes in pregnancy-induced hypertension (PIH) by cross-mating transgenic mice carrying the human-angiotensinogen gene with mice bearing the human-renin gene. Further, we examined antihypertensive effects of four drugs in PIH model mice.Materials and Methods : The systolic blood pressure was measured by the tail-cuff method during the early, mid, and late periods of pregnancy in the transgenic mice and the wild type as control mice. The fetus, placenta, maternal kidney, heart and blood were obtained from the pregnant mice on 18^<th> day of gestation, and then the concentrations of human(h)-renin and angiotensin (AT) II in those materials were measured by radioimmunoassay. Further, the changes of systolic blood pressure and fetal weight in PIH model mice after oral administration of quinapril, candesartan cilexetil, hydralazine and nicardipine were analyzed.Results : In the transgenic mice, the systolic blood pressure began to rise at mid period of gestation, and reached high level in the day before delivery. The hypertension during pregnancy returned to healthy level after delivery. The kidney and fetal weight in the transgenic mice were significantly lower than those in the wild type, but there was no difference in the heart and the placental weight. The hypertension and lower fetal weigh in PIH model mice were improved by oral administration of quinapril and candesartan cilexetil. In the transgenic mice, the h-renin was only detected in the placenta and maternal plasma, and the concentrations of the placental and plasma AT II were significantly higher than those in control mice.Conclusions : Our study showed that the redundant increase of the concentrations of the placental and plasma h-renin and AT II caused hypertension in late period of pregnancy in the transgenic mice.