1. The response of the isolated rat kidney to a mixed amino acid solution was examined in the presence of three renal autacoid inhibitors, indomethacin (a cyclo-oxygenase inhibitor), sulpiride (a dopamine antagonist) and l -nitroarginine methyl ester (an inhibitor of nitric oxide synthesis). 2. Increasing the concentration of the mixed amino acid solution perfusing the kidney from 2 to 8 mmol/l ( n = 6) produced a sustained increase in renal perfusate flow ( P < 0.01) and reversed the time-dependent fall in [ 14 C]inulin clearance ( P < 0.01) demonstrated in kidneys perfused with 2 mmol/l mixed amino acids alone. A significant increase in the fractional sodium reabsorption and decrease in the fractional albumin excretion was also observed. 3. Indomethacin (10 −4 mol/l, n = 6) produced partial (50%) inhibition of the effect of mixed amino acids on [ 14 C]inulin clearance, but did not influence their ability to increase renal perfusate flow. 4. Sulpiride (0.7 μmol min −1 kg −1 , n = 6) produced partial inhibition of the effect of mixed amino acids on both [ 14 C]inulin clearance and renal perfusate flow by 60% and 50%, respectively. Sulpiride also entirely inhibited the reduction in fractional albumin excretion. 5. l -Nitroarginine methyl ester (10 −4 mol/l, n = 6) completely inhibited the effect of mixed amino acids on [ 14 C]inulin clearance, but did not inhibit the increase in renal perfusate flow, even though the basal vascular resistance was markedly enhanced. l -Nitroarginine methyl ester also inhibited the increase in fractional sodium reabsorption produced by the mixed amino acids. 6. It is concluded that prostaglandins, dopamine and nitric oxide may all have a role to play in the direct effect of mixed amino acids on renal function. This does not, however, preclude further modification by additional stimuli generated in vivo.

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 [ 14 C]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 [ 14 C]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 [ 14 C]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 [ 14 C]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.

1. We studied the relation between immunopathology and progressive renal failure after nephrotoxic nephritis (NTN) in rats. 2. Thirty days after induction of nephritis by injection of rabbit anti-rat nephrotoxic serum, pairs of kidneys from 13 nephritic rats were transplanted into separate syngeneic recipients, one of whom had been pre-immunized with rabbit immunoglobulin G (IgG) whilst the other was naive. 3. Progression to renal failure of the transplanted nephritic kidney was studied after removal of the recipient's own kidneys; results from right and left kidney from a single donor in pre-immunized and naive recipients were compared. 4. There were substantial differences in autologous anti-rabbit IgG titres in naive and pre-immunized recipients; despite this pairs of kidneys from the same donor had almost identical courses as assessed by proteinuria, serum creatinine and graft survival. 5. There was substantial variation in survival of kidneys from different donors. But there were very strong correlations of graft survival with proteinuria ( r = 0.97, t = 4.443, P <0.001) and reciprocal serum creatinine ( r = 0.95, t = 4.32, P <0.001) in donors shortly before transplantation. 6. We conclude that autologous antibody titres did not influence the progression to renal failure after nephrotoxic nephritis. The rate of progression was already determined at the time of transplantation.

1. We have examined the effect of a low protein diet on the development of glomerular sclerosis and progressive renal failure after subtotal nephrectomies in rats. 2. Two groups of male Sprague-Dawley rats were studied after five-sixths nephrectomy; group 1 were maintained on a normal diet (13.5 g day −1 kg −1 body weight) and group 2 were fed with a low protein diet (6 g day −1 kg −1 body weight). 3. Rats maintained on a low protein diet survived for longer, and had significantly less glomerular sclerosis and significantly greater glomerular filtration rates when the experiment ended after 7 months. 4. We conclude that dietary protein influences favourably the development of glomerular scarring and renal failure after subtotal nephrectomy in rats.