Differential actions of renal ischemic injury on the intrarenal angiotensin system

Allred, Alicia J., Mark C. Chappell, Carlos M. Ferrario, and Debra I. Diz. Differential actions of renal ischemic injury on the intrarenal angiotensin system. Am J Physiol Renal Physiol 279: F636-F645, 2000.--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 [is less than] 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 [is less than] 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 [sup.125]I-labeled [[Sar.sup.1],[Thr.sup.8]ANG II ([sup.125]I-Sarthran) (0.8 nM) revealed a decreased apparent density of ANG receptors ([is greater than] 80% [AT.sub.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 [is less than] 0.05), 49% in the outer cortical tubulointerstitial area (P [is less than] 0.05), and 48% in the inner cortical-outer medullary area of the vasa recta (P [is less than] 0.05). Medullary binding decreased ~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. angiotensin II; angiotensin-(1-7), angiotensin receptors; [AT.sub.1] receptor; [AT.sub.2] receptor; renal ischemia; urinary angiotensins