Brosnihan K Bridget, Neves Liomar A A, Joyner JaNae, Averill David B, Chappell Mark C, Sarao Renu, Penninger Josef, Ferrario Carlos M
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1032, USA.
Hypertension. 2003 Oct;42(4):749-53. doi: 10.1161/01.HYP.0000085220.53285.11. Epub 2003 Jul 21.
Previously we demonstrated that kidney concentration and urinary excretion of angiotensin-(1-7) are increased during normal pregnancy in rats. Since this finding may reflect local kidney production of angiotensin-(1-7), we determined the immunocytochemical distribution of angiotensin-(1-7) and its newly described processing enzyme, ACE2, in kidneys of virgin and 19-day-pregnant Sprague-Dawley rats. Sprague-Dawley rats were killed at the 19th day of pregnancy, and tissues were prepared for immunocytochemical by using a polyclonal antibody to angiotensin- (1-7) or a monoclonal antibody to ACE2. Angiotensin-(1-7) immunostaining was predominantly localized to the renal tubules traversing both the inner cortex and outer medulla. ACE2 immunostaining was localized throughout the cortex and outer medulla and was visualized in the renal tubules of both virgin and pregnant rats. The quantification of angiotensin-(1-7) and ACE2 immunocytochemical staining showed that in pregnant animals, the intensity of the staining increased by 56% and 117%, respectively (P<0.05). This first demonstration of the immunocytochemical distribution of angiotensin-(1-7) and ACE2 in kidneys of pregnant rats shows that pregnancy increases angiotensin-(1-7) immunocytochemical expression in association with increased ACE2 intensity of staining. The findings suggest that ACE2 may contribute to the local production and overexpression of angiotensin-(1-7) in the kidney during pregnancy.
此前我们证明,在大鼠正常妊娠期间,肾脏对血管紧张素 -(1 - 7)的浓缩和尿排泄增加。由于这一发现可能反映了肾脏局部产生血管紧张素 -(1 - 7),我们确定了血管紧张素 -(1 - 7)及其新描述的加工酶ACE2在未孕和妊娠19天的Sprague-Dawley大鼠肾脏中的免疫细胞化学分布。在妊娠第19天处死Sprague-Dawley大鼠,使用抗血管紧张素 -(1 - 7)的多克隆抗体或抗ACE2的单克隆抗体将组织制备用于免疫细胞化学。血管紧张素 -(1 - 7)免疫染色主要定位于穿过内皮质和外髓质的肾小管。ACE2免疫染色定位于整个皮质和外髓质,在未孕和妊娠大鼠的肾小管中均可见。血管紧张素 -(1 - 7)和ACE2免疫细胞化学染色的定量分析表明,在妊娠动物中,染色强度分别增加了56%和117%(P<0.05)。首次对妊娠大鼠肾脏中血管紧张素 -(1 - 7)和ACE2的免疫细胞化学分布进行的证明表明,妊娠与ACE2染色强度增加相关,会增加血管紧张素 -(1 - 7)的免疫细胞化学表达。这些发现表明,ACE2可能在妊娠期间对肾脏中血管紧张素 -(1 - 7)的局部产生和过表达有贡献。