Differential actions of renal ischemic injury on the intrarenal angiotensin system

Citation
Aj. Allred et al., Differential actions of renal ischemic injury on the intrarenal angiotensin system, AM J P-REN, 279(4), 2000, pp. F636-F645
Citations number
50
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
03636127 → ACNP
Volume
279
Issue
4
Year of publication
2000
Pages
F636 - F645
Database
ISI
SICI code
0363-6127(200010)279:4<F636:DAORII>2.0.ZU;2-Y
Abstract
The present study determined the effect of either occlusion of the left ren al artery for 60 min (ischemia) or sham operation on angiotensin (ANG) rece ptors and tissue and urinary levels of ANG peptides between 24 and 72 h rec overy in male Sprague-Dawley rats. At 24 h postischemia, urinary concentrat ions 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 a t 24 h in postischemic kidneys by an average of 63% compared with the contr alateral nonischemic kidney (P < 0.05). Whereas the enzymatic activity of a ngiotensin-converting enzyme and neprilysin was reduced after ischemia, ren al renin activity in ischemic kidneys rose by 74% compared with sham-operat ed 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-o perated rats. Twenty-four hours after ischemia, ANG II receptors decreased by 68% in glomeruli (P < 0.05), 49% in the outer cortical tubulointerstitia l area (P < 0.05), and 48% in the inner cortical-outer medullary area of th e 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 t o 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 m ay 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 is chemia previously reported by others.