Salt intake determines the renal response to L-arginine infusion in normal human subjects

Abstract

Studies in experimental animals have shown that nitric oxide (NO) generation in the kidney from L-arginine participates in adapting renal function to changes in salt intake, but similar studies in human subjects are lacking. Therefore, we compared the infusion of 30 g of L-arginine to 30 g of branched chain amino acids (control), in eight normal human subjects after 5 to 7 days of equilibration to a low salt (LS; 20 mumol.24 hr-1) or high salt (HS; 200 mumol.24 hr-1) intake. Lithium clearance was used as a marker of proximal tubular reabsorption. Compared to the control infusion, L-arginine did not significantly alter blood pressure, inulin or paraaminohippurate clearance, but significantly increased (P < 0.05) the excretion of NO2 + NO3 (NOx) (LS, 157 +/- 46 to 210 +/- 48 mumol.min-1; HS, 138 +/- 30 to 182 +/- 70) and cGMP (LS, 253 +/- 63 to 337 +/- 76 pmol.min-1; HS, 311 +/- 68 to 563 +/- 52). Renal sodium excretion was decreased by L-arginine infusion during the low salt intake (45 +/- 5 to 21 +/- 3 mumol.min-1; P < 0.05) but was increased by L-arginine during the high salt intake (298 +/- 56 to 537 +/- 84 mumol.min-1; P < 0.05). The calculated fractional reabsorption of sodium in the proximal and distal nephrons, as assessed from lithium and sodium clearances, was increased by L-arginine during the low salt intake but was decreased by L-arginine during the high salt intake. L-arginine increased plasma insulin concentration significantly (P < 0.05). This effect was independent of salt intake (LS, 67 +/- 7 to 92 +/- 13 ng.ml-1; HS, 66 +/- 7 to 76 +/- 9 ng.ml-1). L-arginine did not significantly after plasma renin activity. In conclusion, L-arginine increases the excretion of NOx and cGMP and increases plasma insulin, but the effect on sodium excretion depends upon salt intake. L-arginine enhances Na reabsorption in the proximal and distal nephrons during the low salt intake, but inhibits it during the high salt intake. Effects of L-arginine on NO and cGMP may contribute to its effects on Na reabsorption.