The flux of arginine after ischemia-reperfusion in the rat kidney

Abstract

Background: Renal arginine synthesis is regulated by arginine plasma levels. The amino acid arginine is synthesized in the proximal tubule of the kidney. Renal ischemia reperfusion (I-R) injury as seen after shock, trauma and major vascular surgery, leading to acute tubular necrosis, might reduce arginine production.

Methods: Wistar rats received either bovine liver arginase (ASE), to lower arginine plasma levels, or saline (SAL). Following the ASE or SAL infusion, rats were randomized to receive a renal artery clamp for 70 minutes, followed by 150 minutes of reperfusion. Renal arteriovenous blood samples were measured and plasma flow was calculated in the I-R kidney (SAL/I-R and ASE/I-R) and the contralateral kidney (SAL/C-L and ASE/C-L) in order to determine renal arginine metabolism.

Results: Arginase infusion resulted in lower arginine plasma levels compared to SAL treatment (SAL/I-R vs. ASE/I-R, P < 0.005, and SAL/C-L vs. ASE/C-L, P < 0.005). Renal plasma flow was similar for all groups. The kidney switched from arginine production into arginine uptake after ischemia reperfusion (SAL/I-R vs. SAL/C-L, P < 0.01, and ASE/I-R vs. ASE/C-L, P < 0.01). Renal uptake of glutamine and citrulline increased after ischemia reperfusion (SAL/I-R vs. SAL/C-L and ASE/I-R vs. ASE/C-L, both P < 0.01). Histopathological slices of the kidney showed significantly higher counts of hyperchromasia, pyknosis, nuclear fragmentation and mitoses in individual kidney cells after ischemia reperfusion.

Conclusion: Decreased renal arginine production is observed with unilateral ischemia-reperfusion, and this change in arginine flux could contribute to or slow the recovery from the low plasma levels of arginine seen in conditions like trauma, shock, or after vascular procedures.