EFFECT OF AMINO-ACID INFUSION ON RENAL HEMODYNAMICS IN HUMANS - A DOSE-RESPONSE STUDY

We evaluated the dose-response relationship between the plasma amino acid (AA) concentration and renal hemodynamics in eight normal subjects. After an overnight fast, a balanced 10% AA solution was infused for 180 min at five separate infusion rates: 0.5 (group I), 1.0 (group 11), 2.0 (group III), 4.0 (group IV), and 6.0 (group V) ml.kg(-1).min(-1) on separate days. Basal plasma AA concentration was 1.87 +/- 0.1 mmol/l and increased to 2.26 +/- 0.1 (group 1), 2.66 +/- 0.2 (group II), 3.79 +/- 0.5 (group III), 5.81 +/- 0.4 (group IV), and 7.41 +/- 0.4 mmol/l (group V). Basal glomerular filtration rate (GFR) and renal plasma flow (RPF) averaged 95 +/- 4 and 476 +/- 29 ml.1.73 m(-2).min(-1), respectively, and rose to 98 +/- 5 and 506 +/- 40 (group I) [P = not significant (NS)], 102 +/- 3 and 533 +/- 30 (group II) (P < 0.05 vs. basal), 110 +/- 4 and 567 +/- 29 (group III), 115 +/- 7 and 610 +/- 55 (group IV), and 117 +/- 7 and 614 +/- 66 ml.1.73 m(-2).min(-1) (group V) (P = NS vs, group TV). Basal plasma glucagon concentration averaged 68 +/- 10 pg/ml and increased to 74 +/- 10 (group I), 83 +/- 11 (group II) (P < 0.05 vs. basal), 100 +/- 14 (group III), 121 +/- 14 (group IV), and 229 +/- 35 pg/ml (group V) (P < 0.01 vs. basal). Increases in plasma growth hormone (GH) and insulin levels were observed only during groups IV and V. Plasma insulin-like growth factor I (IGF-I) did not change significantly during AA infusion. These results indicate the following: 1) increases in plasma AA concentrations within the physiological range cause a dose-related rise in GFR and RPF (r = 0.94, P < 0.001); 2) pharmacological increases in plasma AA levels are not associated with any further rise in GFR and RPF above that observed with physiological hyperaminoacidemia; and 3) within the physiological range the increases in GFR and RPF are closely correlated with the elevation in plasma glucagon concentration (r = 0.98, P < 0.001) but not with changes in insulin, GH, or IGF-I levels.