Differential actions of renal ischemic injury on the intrarenal angiotensin system

Am J Physiol Renal Physiol. 2000 Oct;279(4):F636-45. doi: 10.1152/ajprenal.2000.279.4.F636.

Abstract

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 (125)I-labeled [Sar(1),Thr(8)]ANG II ((125)I-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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / metabolism
  • Angiotensins / blood
  • Angiotensins / metabolism
  • Angiotensins / urine
  • Animals
  • Diuresis
  • Enzymes / metabolism
  • Ischemia / metabolism*
  • Kidney / physiopathology*
  • Kidney Cortex / enzymology
  • Male
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism
  • Peptide Fragments / urine
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation*
  • Renin-Angiotensin System / physiology*
  • Reperfusion Injury / physiopathology

Substances

  • Angiotensins
  • Enzymes
  • Peptide Fragments
  • Angiotensin II
  • angiotensin II, Sar(1)-Thr(8)-