Differential actions of renal ischemic injury on the intrarenal angiotensin system
Differential actions of renal ischemic injury on the intrarenal angiotensin system
复制标题
DOI：
10.1152/ajprenal.2000.279.4.f636
复制
发表时间：
2000-10-01
影响因子：
4.2
通讯作者：
Diz, DI
中科院分区：
文献类型：
--
作者：
Allred, AJ;Chappell, MC;Diz, DI
本研究测定了雄性Sprague-Dawley大鼠左肾动脉闭塞60 min（缺血）或假手术对血管紧张素（ANG）受体以及24 h和72 h恢复期组织和尿液中ANG肽水平的影响。缺血后24小时，尿液中ANG I和ANG-（1-7）浓度分别平均升高83%和64%（P < 0.05），但到72小时时已降至对照水平。缺血后24 h肾脏组织ANG Ⅱ较对侧非缺血肾脏平均升高63%（P < 0.05）。而血管紧张素转换酶和脑啡肽酶的酶活性在缺血后降低，缺血肾的肾肾素活性上升了74%，与假手术肾相比。使用I-125标记的[Sar（1），Thr（8）]ANG II（I-125-Sarthran）（0.8 nM）进行的受体放射自显影显示，与假手术大鼠的肾脏相比，缺血肾脏中ANG受体的表观密度降低（> 80%AT（1）），对侧非缺血肾脏中的ANG受体的表观密度也有降低的趋势。缺血24 h，肾小球ANG Ⅱ受体下降68%（P < 0.05），外皮质小管间质区下降49%（P < 0.05），内皮质外髓质区下降48%（P < 0.05）。与假手术组相比，缺血性肾脏和对侧非缺血性肾脏的髓质结合率均降低了50%。在缺血肾的所有区域中，受体在72小时恢复到与假手术对照大鼠无差异的水平。阻断后24 h尿ANG I和ANG-（1-7）的显著变化提示这些肽可能是急性肾缺血的潜在尿标志物。缺血性肾脏血管和肾小管区域中受体的减少提供了先前由其他人报道的缺血后对ANG II的血管收缩反应丧失的机制。
The present study determined the effect of either occlusion of the left renal artery for 60 min (ischemia) or sham operation on angiotensin (ANG) receptors and tissue and urinary levels of ANG peptides between 24 and 72 h recovery in male Sprague-Dawley rats. At 24 h postischemia, urinary concentrations of ANG I and ANG-(1-7) rose by an average of 83 and 64%, respectively (P < 0.05) but had declined to control levels by 72 h. Tissue ANG II rose at 24 h in postischemic kidneys by an average of 63% compared with the contralateral nonischemic kidney (P < 0.05). Whereas the enzymatic activity of angiotensin-converting enzyme and neprilysin was reduced after ischemia, renal renin activity in ischemic kidneys rose by 74% compared with sham-operated kidneys. Receptor autoradiography using I-125-labeled [Sar(1),Thr(8)]ANG II ( I-125-Sarthran) (0.8 nM) revealed a decreased apparent density of ANG receptors (>80% AT(1)) in ischemic kidneys with a trend for a decrease in the contralateral nonischemic kidneys compared with the kidneys from sham-operated rats. Twenty-four hours after ischemia, ANG II receptors decreased by 68% in glomeruli (P < 0.05), 49% in the outer cortical tubulointerstitial area (P < 0.05), and 48% in the inner cortical-outer medullary area of the vasa recta (P < 0.05). Medullary binding decreased similar to 50% in both the ischemic kidney and the contralateral nonischemic kidney compared with sham. In all regions of the ischemic kidney, receptors recovered by 72 h to levels not different from sham control rats. The marked change in urinary ANG I and ANG-(1-7) at 24 h following occlusion indicates these peptides may be potential urinary markers for acute renal ischemia. The reduction of receptors in vascular and tubular regions of the ischemic kidney provides a mechanism for the loss of vasoconstrictor responses to ANG II following ischemia previously reported by others.