Joyner J, Neves L A A, Granger J P, Alexander B T, Merrill D C, Chappell M C, Ferrario C M, Davis W P, Brosnihan K B
The Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1032, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R169-77. doi: 10.1152/ajpregu.00387.2006. Epub 2007 Apr 11.
We recently demonstrated that renin-angiotensin system (RAS) overactivity during late gestation in rats is associated with increased kidney and urine levels of ANG-(1-7) and enhanced kidney immunostaining of ANG-(1-7) and angiotensin-converting enzyme 2 (ACE2). To understand the temporal-spatial changes in normal and hypertensive pregnancies, the renal distribution of ANG-(1-7) and ACE2 in association with kidney angiotensin peptides and ACE2 activity was examined in virgin, normal pregnant (NP; gestational days 5, 15, and 19) and reduced uterine perfusion pressure (RUPP at day 19) pregnant Sprague-Dawley rats. ANG-(1-7) and ACE2 immunocytochemical staining increased 1.8- and 1.9-fold and 1.7- and 1.8-fold, respectively, at days 15 and 19 of NP, compared with virgin rats. ANG-(1-7) and ANG II concentrations were increased in the kidney at 19 days of gestation. ACE2 activity measured using a fluorescent substrate was increased 1.9- and 1.9-fold in the cortex and 1.9- and 1.8-fold in the medulla at days 15 and 19 of NP. In the RUPP animals, ANG-(1-7) immunostaining and concentration were significantly decreased compared with 19-day NP rats. ACE2 activity was unchanged in the cortex and medulla of RUPP rats. In conclusion, during NP, the concurrent changes of ACE2 and ANG-(1-7) suggest that ACE2 plays an important role in regulating the renal levels of ANG-(1-7) at mid to late gestation. However, the decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes during hypertensive pregnancy.
我们最近证明，大鼠妊娠晚期肾素-血管紧张素系统（RAS）过度活跃与肾脏和尿液中ANG-(1-7)水平升高以及肾脏中ANG-(1-7)和血管紧张素转换酶2（ACE2）免疫染色增强有关。为了解正常和高血压妊娠期间的时空变化，在未孕、正常妊娠（NP；妊娠第5、15和19天）以及子宫灌注压降低（第19天的RUPP）的妊娠Sprague-Dawley大鼠中，研究了ANG-(1-7)和ACE2与肾脏血管紧张素肽和ACE2活性相关的肾脏分布情况。与未孕大鼠相比，NP妊娠第15天和19天时，ANG-(1-7)和ACE2免疫细胞化学染色分别增加了1.8倍和1.9倍以及1.7倍和1.8倍。妊娠第19天时，肾脏中ANG-(1-7)和ANG II浓度升高。使用荧光底物测量的ACE2活性在NP妊娠第15天和19天时，皮质中增加了1.9倍和1.9倍，髓质中增加了1.9倍和1.8倍。在RUPP动物中，与19天的NP大鼠相比，ANG-(1-7)免疫染色和浓度显著降低。RUPP大鼠皮质和髓质中的ACE2活性未发生变化。总之，在NP期间，ACE2和ANG-(1-7)的同时变化表明ACE2在妊娠中后期调节肾脏中ANG-(1-7)水平方面发挥重要作用。然而，在ACE2未伴随降低的情况下肾脏ANG-(1-7)含量降低，提示在高血压妊娠期间其他ANG-(1-7)形成或降解酶参与其中。
