aDivision of Medical Biology, Department of Pathology and Medical Biology bDivision of Nephrology, Department of Internal Medicine cDepartment of Obstetrics & Gynecology dDivision of Pathology, Department of Pathology and Medical Biology eMedical Faculty of the Charité fDepartment of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Hypertens. 2017 Dec;35(12):2468-2478. doi: 10.1097/HJH.0000000000001474.
Formerly preeclamptic women have an increased risk for cardiovascular and renal disease later in life. It is unknown which mechanisms contribute to this increased risk and whether this is induced by preeclampsia or by prepregnancy factors. We hypothesized that the increased risk for cardiovascular disease is partly due to an increased angiotensin II (ang II) responsiveness postpartum and that preeclampsia itself is involved in inducing this increased ang II responsiveness.
In never-pregnant, formerly healthy pregnant rats and rats with former experimental preeclampsia [experimental preeclampsia model induced by low-dose endotoxin infusion on day 14 of pregnancy; endotoxin-infused pregnant rats (EP-rats)], ang II responsiveness was studied by measuring changes in blood pressure (BP) and proteinuria after chronic ang II infusion with osmotic minipumps (200 ng/kg per min). In addition, we measured BP and responses to ang II (0.3, 1.0 and 3.0 ng/kg per min) in 18 formerly early-onset preeclamptic, without comorbidities, and 18 formerly healthy pregnant women (controls).
In rats, a significantly higher systolic BP at termination was observed in formerly EP-rats vs. never-pregnant rats after ang II infusion (159.5 ± 29.5 vs. 136.7 ± 16.8; P = 0.049). In response to ang II, there was a significant increase in proteinuria in formerly EP-rats vs. healthy pregnant and never-pregnant rats (P < 0.01 for both). In humans, 1.0 ng/kg per min ang II showed a trend towards an increased mean arterial BP response in formerly preeclamptic women vs. controls (P = 0.057).
Our data show an increased ang II responsiveness following (experimental) preeclampsia and support a role for preeclampsia itself in altered ang II responsiveness postpartum.
曾患有先兆子痫的女性在以后的生活中患心血管和肾脏疾病的风险增加。目前尚不清楚哪些机制导致了这种风险的增加，以及这种风险是由先兆子痫还是由孕前因素引起的。我们假设，心血管疾病风险的增加部分是由于产后血管紧张素 II（ang II）反应性增加，而先兆子痫本身参与诱导这种 ang II 反应性增加。
在从未怀孕、曾健康妊娠的大鼠和曾患有实验性先兆子痫的大鼠（通过在妊娠第 14 天给予低剂量内毒素输注诱导的实验性先兆子痫模型；内毒素输注妊娠大鼠（EP-rat））中，通过测量慢性 ang II 输注后血压（BP）和蛋白尿的变化来研究 ang II 反应性（通过渗透微型泵以 200ng/kg/min 的速度输注）。此外，我们还测量了 18 名曾患有早发型先兆子痫、无合并症的妇女（对照组）和 18 名曾健康妊娠的妇女的 BP 以及对 ang II（0.3、1.0 和 3.0ng/kg/min）的反应。
在大鼠中，与从未怀孕的大鼠相比，在 ang II 输注后，曾患有 EP-rat 的大鼠的收缩压在终止时明显升高（159.5±29.5 与 136.7±16.8；P=0.049）。在对 ang II 的反应中，曾患有 EP-rat 的大鼠的蛋白尿明显增加，而健康妊娠和未怀孕的大鼠则没有（两者均 P<0.01）。在人类中，1.0ng/kg/min 的 ang II 显示出曾患有先兆子痫的妇女与对照组相比平均动脉压反应增加的趋势（P=0.057）。
我们的数据显示，（实验性）先兆子痫后 ang II 反应性增加，并支持先兆子痫本身在产后 ang II 反应性改变中的作用。
