A new mouse model for pregnancy-induced hypertension.

妊娠高血压综合征(PIH)是妊娠最常见和最严重的并发症，通常在妊娠晚期出现，其病理生理机制仍不清楚[1]。在这里，我们表明，只有当表达人血管紧张素原的转基因雌性小鼠与携带人类肾素基因的雄性小鼠交配时，怀孕后期的血压才会显著升高，这是由于胎儿胎盘中的人肾素分泌到母体循环中。观察到的一过性血压升高在分娩后迅速恢复到非妊娠状态。组织病理学检查显示肾小球均匀增大，伴有尿蛋白排泄增加，胎盘心肌肥大、坏死和水肿。这些结果清楚地表明，导致母体发病率和死亡率的妊高征是由转基因小鼠中雄性小鼠胎盘肾素与母体血管紧张素原的组合作用触发的。

Pregnancy-induced hypertension (PIH), the commonest and most serious complications of pregnancy, usually becomes apparent in late pregnancy, the pathophysiology of which has remained elusive (1). Here, we show that later in pregnancy blood pressure is dramatically elevated in transgenic female mice expressing human angiotensinogen only when mated with male mice carrying the human renin gene, which is due to the secretion of feto-placental human renin into the maternal circulation. The observed transient elevation of blood pressure was sharply returned to the non-pregnant state after delivery. Histopathologic examinations revealed uniform enlargement of glomeruli associated with increase in urinary protein excretion, myocardial hypertrophy and necrosis and edema in placenta. These results clearly demonstrate that PIH that caused maternal morbidity and mortality is triggered by the combinatorial action of feto-placental renin genetically derived from male mice with maternal angiotensinogen in transgenic mice.