Renal cellular response to ureteral obstruction: role of maturation and angiotensin II
Renal cellular response to ureteral obstruction: role of maturation and angiotensin II
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DOI：
10.1152/ajprenal.1999.277.1.f41
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发表时间：
1999-07-01
影响因子：
4.2
通讯作者：
Wolstenholme, JT
中科院分区：
文献类型：
--
作者：
Chevalier, RL;Thornhill, BA;Wolstenholme, JT
肾血管紧张素II（ANG II）增加是单侧输尿管梗阻（WO）的结果，在出生后早期，血管紧张素AT（2）受体比AT（1）受体占优势。为了检查新生和成年大鼠对3天WO的肾细胞反应，氯沙坦和PD-123319分别抑制AT（1）和AT（2）受体。其他大鼠接受外源性ANG II，0.5 mg.kg（-1）.天（-1）。增殖细胞核抗原和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记技术分别定量检测肾细胞增殖和凋亡。在新生儿中，UUO减少了增殖，增加了肾小管凋亡。氯沙坦没有检测到细胞效应，而PD-123319增加细胞增殖和抑制凋亡，外源性ANG II刺激凋亡。在成人中，UUO增加细胞增殖以及凋亡，而氯沙坦，PD-123319和外源性ANG II没有改变细胞反应。总之，WO通过减少增殖和刺激凋亡，至少部分通过血管紧张素AT（2）受体，损害新生儿的肾脏生长。WO刺激成人肾细胞增殖和细胞凋亡，但这些作用与ANG II无关。我们推测，发育中的肾脏对尿路梗阻的独特早期反应是由高度活化的肾素-血管紧张素系统和AT（2）受体的优势介导的。
Renal angiotensin II (ANG II) is increased as a result of unilateral ureteral obstruction (WO), and angiotensin AT(2) receptors predominate over AT(1) receptors in the early postnatal period. To examine the renal cellular response to 3-day WO in the neonatal and adult rat, AT(1) and AT(2) receptors were inhibited by losartan and PD-123319, respectively. Additional rats received exogenous ANG II, 0.5 mg.kg(-1).day(-1). Renal cellular proliferation and apoptosis were quantitated by proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling technique, respectively. In the neonate, UUO reduced proliferation and increased tubular apoptosis. Losartan had no detectable cellular effect, whereas PD-123319 increased cellular proliferation and suppressed apoptosis, and exogenous ANG II stimulated apoptosis. In the adult, UUO increased cellular proliferation as well as apoptosis, whereas losartan, PD-123319, and exogenous ANG II did not alter the cellular response. In conclusion, WO impairs renal growth in the neonate by reducing proliferation and stimulating apoptosis, at least in part through angiotensin AT(2) receptors. WO stimulates both renal cellular proliferation and apoptosis in the adult, but these effects are independent of ANG II. We speculate that the unique early responses of the developing kidney to urinary tract obstruction are mediated by a highly activated renin-angiotensin system and preponderance of AT(2) receptors.