Renal arginine synthesis is impaired after experimental ischaemia–reperfusion

Abstract Background Endogenous arginine synthesis is important for maintaining normal plasma levels of arginine. Recently it was shown that low plasma levels of arginine are the drive for renal arginine synthesis. In chronic renal insufficiency low plasma levels of arginine are common. To evaluate renal arginine synthesis in acute renal injury, as seen after periods of ischaemia during major vascular surgery, ischaemia–reperfusion of one kidney was performed in a rat model. Methods In this model of unilateral renal ischaemia–reperfusion male Wistar rats were used. Arginase infusion (ASE) was used to lower arginine plasma levels to 50 per cent of normal and control rats received saline infusion (SAL). After an ischaemic period of 90 min, the kidney was perfused for 150 min (IR kidney). The contralateral kidney was left in situ and served as a control (CL kidney). Blood flow measurement was performed at the end of the experiment using radiolabelled microspheres. Blood samples were taken for amino acid analysis (high-pressure liquid chromatography). Uptake or release of arginine (flux) was calculated from flow and the arteriovenous concentration difference. Results Infusion of arginase efficiently decreased arginine plasma levels (ASE: mean(s.d.) 45·3(4·8) μmol/dm3 versus SAL: 107·5(6·0); P < 0·0001). In SAL rats, in both IR and CL kidneys a net uptake of arginine was observed (arginine flux CL kidney: + 12·5(4·9), IR kidney: + 23·6(5·8) μmol/dm3; P not significant). Lowering arginine plasma levels by arginase resulted in production of arginine in the (non-ischaemic) CL kidney. In contrast, in the IR kidney a net uptake of arginine was seen (arginine flux CL kidney: − 5·3(2·2) μmol/dm3, IR kidney: + 10·3(3·7) μmol/dm3; P < 0·01). Conclusion Synthesis of arginine by the kidney was impaired after a period of acute ischaemia–reperfusion. Ischaemia–reperfusion injury of the kidney is a condition often seen after major vascular reconstruction and impaired arginine synthesis might limit substrate for the l-arginine nitric oxide pathway.