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

Abstract

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. 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. 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. 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.