Hypertension and Vascular Research Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1032, USA.
Hypertension. 2011 Nov;58(5):852-8. doi: 10.1161/HYPERTENSIONAHA.111.179358. Epub 2011 Oct 3.
Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system that influences the relative expression of angiotensin II (Ang II) and Ang-(1-7). Although ACE2 expression increases in normal pregnancy, the impact of ACE2 deficiency in pregnancy has not been elucidated. We determined the influence of ACE2 deficiency on circulating and tissue renin-angiotensin system components, fetal and maternal growth characteristics, and maternal hemodynamics (mean blood pressure and cardiac output) at day 18 of gestation. Gestational body weight gain was lower in the ACE2 knockout (KO) versus C57BL/6 (wild-type) mice (30.3±4.7 versus 38.2±1.0 g; P<0.001). Fetal weight (0.94±0.1 versus 1.24±0.01 g; P<0.01) and length (19.6±0.2 versus 22.2±0.2 mm; P<0.001) were less in KO. Mean blood pressure was significantly reduced in C57BL/6 with pregnancy; it was elevated (P<0.05) in the KO virgin and pregnant mice, and this was associated with an increased cardiac output in both C57BL/6 and KO pregnant mice (P<0.05). Plasma Ang-(1-7) was reduced in pregnant KO mice (P<0.05). Placenta Ang II levels were higher in KO mice (52.9±6.0 versus 22.0±3.3 fmol/mg of protein; P<0.001). Renal Ang II levels were greater in KO virgin mice (30.0±1.7 versus 23.7±1.1 fmol/mg of protein; P<0.001). There was no change in the Ang-(1-7) levels in the KO placenta and virgin kidney. These results suggest that ACE2 deficiency and associated elevated placenta Ang II levels impact pregnancy by impairing gestational weight gain and restricting fetal growth.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素系统的关键酶，影响血管紧张素 II（Ang II）和 Ang-（1-7）的相对表达。尽管 ACE2 在正常妊娠中表达增加，但 ACE2 缺乏对妊娠的影响尚未阐明。我们确定了 ACE2 缺乏对循环和组织肾素-血管紧张素系统成分、胎儿和母体生长特征以及妊娠 18 天母体血液动力学（平均血压和心输出量）的影响。ACE2 敲除（KO）与 C57BL/6（野生型）小鼠相比，妊娠期间体重增加较低（30.3±4.7 与 38.2±1.0 g；P<0.001）。胎儿体重（0.94±0.1 与 1.24±0.01 g；P<0.01）和长度（19.6±0.2 与 22.2±0.2 mm；P<0.001）也较低 KO。C57BL/6 妊娠时平均血压显著降低；KO 处女和妊娠小鼠的血压升高（P<0.05），并且这种升高与 C57BL/6 和 KO 妊娠小鼠的心输出量增加有关（P<0.05）。妊娠 KO 小鼠的血浆 Ang-（1-7）减少（P<0.05）。KO 小鼠的胎盘 Ang II 水平较高（52.9±6.0 与 22.0±3.3 fmol/mg 蛋白；P<0.001）。KO 处女小鼠的肾脏 Ang II 水平更高（30.0±1.7 与 23.7±1.1 fmol/mg 蛋白；P<0.001）。KO 胎盘和处女肾中的 Ang-（1-7）水平没有变化。这些结果表明，ACE2 缺乏和相关的胎盘 Ang II 水平升高通过损害妊娠体重增加和限制胎儿生长来影响妊娠。
