Differential Effects of Amino Acids on the Isolated Perfused Rat Kidney

1. The direct effects of individual amino acids, including glycine (a neutral amino acid), l-glutamic acid (an acidic amino acid), l-leucine (a neutral, branched-chain amino acid) and l-arginine (a basic amino acid), on renal function were compared with a mixed amino acid solution by using the isolated rat kidney perfused with a physiological saline solution containing 6.7% (w/v) albumin and a basal level of 2 mmol/l mixed amino acids.

2. In a control series, the renal perfusate flow was stable but the glomerular filtration rate, as measured by [¹⁴C]inulin clearance, declined with time. A stable glomerular filtration rate could be obtained by increasing the basal perfusate amino acid concentration to 14 mmol/l.

3. The addition of 6 mmol/l mixed amino acids produced a sustained increase in renal perfusate flow and an increase in [¹⁴C]inulin clearance, reversing its time-dependent fall. Sodium reabsorption was enhanced, but, unlike the control series, no increase in fractional albumin excretion was obtained.

4. Renal perfusate flow was increased by glycine (6 mmol/l), l-arginine hydrochloride (6 mmoll) and sodium glutamate (6 mmol/l) but remained unaffected by l-leucine. The vasodilatation induced by l-arginine hydrochloride and sodium glutamate was not sustained.

5. The time-dependent fall in [¹⁴C]inulin clearance was prevented by glycine, l-arginine and glutamic acid, but not by l-leucine. l-Arginine hydrochloride, like the mixed amino acid solution, produced a significant increase in [¹⁴C]inulin clearance.

6. The fractional reabsorption of sodium was increased by glycine and l-leucine, was unaffected by sodium glutamate and was decreased by l-arginine hydrochloride. The time-dependent fall in the fractional excretion of albumin seen in the control series was, however, reversed by all individual amino acids.

7. The results indicate that amino acids can produce renal vasodilatation and hyperfiltration by a direct effect on the kidney, independent of the release of systemic hormones. Individual amino acids, however, differ in their contribution to the response elicited by a mixed amino acid solution. The use of individual amino acids to mimic the renal response to dietary protein in vivo may therefore be inappropriate.