Department of Physiology and Hypertension and Renal Center, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Am J Physiol Renal Physiol. 2011 Mar;300(3):F749-55. doi: 10.1152/ajprenal.00383.2009. Epub 2011 Jan 5.
Alterations in the balance between ANG II/ACE and ANG 1-7/ACE2 in ANG II-dependent hypertension could reduce the generation of ANG 1-7 and contribute further to increased intrarenal ANG II. Upregulation of collecting duct (CD) renin may lead to increased ANG II formation during ANG II-dependent hypertension, thus contributing to this imbalance. We measured ANG I, ANG II, and ANG 1-7 contents, angiotensin-converting enzyme (ACE) and ACE2 gene expression, and renin activity in the renal cortex and medulla in the clipped kidneys (CK) and nonclipped kidneys (NCK) of 2K1C rats. After 3 wk of unilateral renal clipping, systolic blood pressure and plasma renin activity increased in 2K1C rats (n = 11) compared with sham rats (n = 9). Renal medullary angiotensin peptide levels were increased in 2K1C rats [ANG I: (CK = 171 ± 4; NCK = 251 ± 8 vs. sham = 55 ± 3 pg/g protein; P < 0.05); ANG II: (CK = 558 ± 79; NCK = 328 ± 18 vs. sham = 94 ± 7 pg/g protein; P < 0.001)]; and ANG 1-7 levels decreased (CK = 18 ± 2; NCK = 19 ± 2 pg/g vs. sham = 63 ± 10 pg/g; P < 0.001). In renal medullas of both kidneys of 2K1C rats, ACE mRNA levels and activity increased but ACE2 decreased. In further studies, we compared renal ACE and ACE2 mRNA levels and their activities from chronic ANG II-infused (n = 6) and sham-operated rats (n = 5). Although the ACE mRNA levels did not differ between ANG II rats and sham rats, the ANG II rats exhibited greater ACE activity and reduced ACE2 mRNA levels and activity. Renal medullary renin activity was similar in the CK and NCK of 2K1C rats but higher compared with sham. Thus, the differential regulation of ACE and ACE2 along with the upregulation of CD renin in both the CK and NCK in 2K1C hypertensive rats indicates that they are independent of perfusion pressure and contribute to the altered content of intrarenal ANG II and ANG 1-7.
在血管紧张素 II（ANG II）依赖性高血压中，ANG II/ACE 和 ANG 1-7/ACE2 之间的平衡改变可能会减少 ANG 1-7 的生成，并进一步导致肾内 ANG II 增加。集合管（CD）肾素的上调可能导致 ANG II 依赖性高血压期间 ANG II 的形成增加，从而导致这种失衡。我们测量了 2K1C 大鼠夹闭侧肾脏（CK）和未夹闭侧肾脏（NCK）的肾皮质和髓质中的血管紧张素 I（ANG I）、血管紧张素 II（ANG II）和 ANG 1-7 含量、血管紧张素转换酶（ACE）和 ACE2 基因表达以及肾素活性。在单侧肾夹闭 3 周后，与假手术大鼠（n = 9）相比，2K1C 大鼠的收缩压和血浆肾素活性升高（n = 11）。2K1C 大鼠的肾髓质血管紧张素肽水平升高[ANG I：（CK = 171 ± 4；NCK = 251 ± 8 与 sham = 55 ± 3 pg/g 蛋白；P < 0.05）；ANG II：（CK = 558 ± 79；NCK = 328 ± 18 与 sham = 94 ± 7 pg/g 蛋白；P < 0.001）]；而 ANG 1-7 水平降低（CK = 18 ± 2；NCK = 19 ± 2 pg/g 与 sham = 63 ± 10 pg/g；P < 0.001）。在 2K1C 大鼠双侧肾脏的肾髓质中，ACE mRNA 水平和活性增加，但 ACE2 减少。在进一步的研究中，我们比较了慢性 ANG II 输注（n = 6）和假手术大鼠（n = 5）的肾 ACE 和 ACE2 mRNA 水平及其活性。尽管 ANG II 大鼠和假手术大鼠的 ACE mRNA 水平没有差异，但 ANG II 大鼠表现出更高的 ACE 活性和降低的 ACE2 mRNA 水平和活性。2K1C 大鼠 CK 和 NCK 的肾髓质肾素活性相似，但高于假手术组。因此，2K1C 高血压大鼠 CK 和 NCK 中 ACE 和 ACE2 的差异调节以及 CD 肾素的上调表明它们独立于灌注压，并有助于改变肾内 ANG II 和 ANG 1-7 的含量。
