ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE RENAL HEMODYNAMIC-RESPONSE TO AMINO-ACID INFUSION

The present study was performed in anesthetized rats to compare the renal hemodynamic responses to mixed amino acids (M-AA) with those to L-arginine (L-Arg) and to examine the effect of endothelium-derived nitric oxide (EDNO) synthesis blockade on the M-AA-induced rise in renal plasma flow (RPF) and glomerular filtration rate (GFR). Intravenous infusion of both M-AA (Ser, Gly, Ala, and Pro, 0.71 mmol.100 g-1.min-1) and L-Arg (0.71 mmol.100 g-1.min-1) increased RPF and GFR. Peak increases in RPF for M-AA and L-Arg were 39.7% (P < 0.05) and 63.4% (P < 0.01), whereas GFR increases were 33.6% (P < 0.05) and 46.7% (P < 0.01, respectively). Outer cortical blood flow (OCBF) was increased with both treatments. Sodium excretion and urine flow were increased more with L-Arg than M-AA (both P < 0.01). Infusion of the nitric oxide synthesis inhibitor, nitro-L-arginine (N-L-Arg, 20 mug.100 g-1.min-1) increased mean arterial pressure but decreased RPF 48.4% (P < 0.001), OCBF 39.5% (P < 0.001), GFR 37.8% (P < 0.01), urine flow 29.8% (P < 0.01), and sodium excretion 40.9% (P < 0.01). When M-AA was administered after N-L-Arg, significant increases in OCBF, RPF, and GFR were observed (P < 0.01); there was also an enhancement of sodium excretion and urine flow (both P < 0.05). In addition, during co-infusion of M-AA and N-L-Arg, renal hemodynamics and excretory function values were significantly greater than those obtained during N-L-Arg alone. These results provide further evidence that EDNO alters the baseline level of renal hemodynamics. However, the enhancement of OCBF, RPF, GFR, urine flow, and sodium excretion by M-AA during EDNO blockade suggests that mechanisms in addition to EDNO contribute to the renal responses to amino acid infusion.