Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes
Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes
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DOI：
10.1152/ajprenal.00656.2011
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发表时间：
2012-06-01
影响因子：
4.2
通讯作者：
Chappell, Mark C.
中科院分区：
文献类型：
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作者：
Yamaleyeva, Liliya M.;Gilliam-Davis, Shea;Chappell, Mark C.
Yamaleyeva LM、吉列姆-戴维斯 S、阿尔梅达 I、布罗斯尼汉 KB、林赛 SH、查佩尔 MC。患有早发性糖尿病的高血压 mRen2.Lewis 大鼠中循环和肾脏 ACE2 和 ACE 的差异调节。 Am J Physiol Renal Physiol 302：F1374-F1384，2012。首次发表于 2012 年 2 月 29 日； doi:10.1152/ajprenal.00656.2011.-我们研究了早期糖尿病对雄性和雌性 mRen2.Lewis (mRen2) 高血压大鼠循环和肾脏肾素血管紧张素系统 (RAS) 的影响。 11 周龄时用链脲佐菌素 (STZ；65 mg/kg) 诱导糖尿病 (DB)，持续 4 周，无需补充胰岛素。与对照组（CON）相比，DB 男性或女性的收缩压没有升高。 DB 女性中循环血管紧张素转换酶 2 (ACE2) 增加九倍 (P < 0.05)，DB 男性中增加三倍 (P < 0.05)，但 DB 组中循环 ACE 和 ANG II 较高。 DB 雌性的血清 C 反应蛋白升高，但 DB 雄性的血清 C 反应蛋白没有升高，并且 DB 雌性的血管对乙酰胆碱和雌二醇的反应减弱。 DB 女性和男性的蛋白尿、白蛋白尿和血管紧张素原排泄量增加程度相似。两个 DB 组的肾小球 VEGF 表达也增加到相似的程度。肾脏炎症（CD68（+）细胞）仅在 DB 雌性中增加，尽管雄性表现出更严重的炎症，这与 DB 没有不同。皮质 ACE2 在 DB 女性中没有变化，但在 DB 男性中减少了 (30%)。 DB 女性的肾中性溶酶活性 (>75%, P < 0.05) 显着低于 DB 和 CON 男性。女性（75%，P < 0.05）和男性（50%；P < 0.05）DB 组的 ACE 活性均显着降低，而皮质 ANG II 和 Ang-(1-7) 水平没有变化。总之，尽管循环 ACE2 显着增加且肾脏内 ACE 显着减少，但雌性 mRen2 大鼠在早期 STZ 诱导的糖尿病中并未免受血管损伤、肾脏炎症和肾损伤的影响。
Yamaleyeva LM, Gilliam-Davis S, Almeida I, Brosnihan KB, Lindsey SH, Chappell MC. Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes. Am J Physiol Renal Physiol 302: F1374-F1384, 2012. First published February 29, 2012; doi:10.1152/ajprenal.00656.2011.-We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold (P < 0.05) in DB females and threefold (P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68(+) cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney.