Rats transgenic for human renin and human angiotensinogen as a model for gestational hypertension
Rats transgenic for human renin and human angiotensinogen as a model for gestational hypertension
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DOI：
10.1681/asn.v11112056
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发表时间：
2000-11-01
影响因子：
13.6
通讯作者：
Luft, FC
中科院分区：
文献类型：
--
作者：
Bohlender, J;Ganten, D;Luft, FC
妊娠期高血压的动物模型是有问题的，先前描述了一种新的小鼠模型。该研究中的母鼠为人血管紧张素原转基因动物，母鼠为人肾素转基因动物;人肾素在胎盘中表达并由胎盘产生。该模型适用于大鼠，其在慢性器械和生理测量方面具有更大的实用性。人血管紧张素原转基因雌性大鼠与人肾素转基因大鼠交配。妊娠第5天遥测血压从110/80 mmHg升高至180/140 mmHg，而心率略有增加。在胎盘中表达了肾素转基因，这导致人血浆肾素浓度从0增加到937 +/- 800 ng血管紧张素I ml/h;分娩后该值恢复到0。相反，与转人血管紧张素原基因的雄性大鼠交配的转人肾素基因的雌性大鼠表现出血压降低。在这些大鼠中，血浆中的人血管紧张素原仍然检测不到。这些转基因大鼠的双转基因后代患上了高血压和终末器官损伤，无论转基因的来源如何。结论是，携带人肾素和血管紧张素原基因的转基因大鼠是一种有吸引力的妊娠高血压模型。大鼠模型将比小鼠模型具有更大的实用性。
Animal models of gestational hypertension are problematic, A novel mouse model was described earlier. The dams in that study were transgenic for human angiotensinogen and the sires for human renin; human renin was expressed in and produced by the placenta. This model was adapted to the rat, which has greater utility in terms of chronic instrumentation and physiologic measurements. Female rats transgenic for human angiotensinogen were mated with rats transgenic for human renin. Telemetry BP increased on day 5 of pregnancy from 110/80 mmHg to as high as 180/140 mmHg, while heart rate increased slightly. The renin transgene was expressed in the placenta, which resulted in increased human plasma renin concentration from 0 to 937 +/- 800 ng angiotensin I ml/h; the values returned to 0 after delivery. Female rats transgenic for human renin that were mated with male rats transgenic for human angiotensinogen in contrast exhibited a decrease in BP. In these rats, human angiotensinogen in plasma remained undetectable. Double transgenic offspring of these transgenic rats developed hypertension and end-organ damage, regardless of the source of the transgenes. The conclusion is that transgenic rats that bear human renin and angiotensinogen genes make an attractive model for gestational hypertension. The rat model will have greater utility than the mouse model.