Assessment of endothelial function of the renal vasculature in human subjects

Background -Arginine, the substrate of nitric oxide (NO) synthase, and NG-monomethyl- -arginine (L-NMMA), a competitive inhibitor of endothelial NO synthase, are used to analyze endothelial function of the renal vasculature. However, little is known about the appropriate dose of -arginine to be used and the duration of action of arginine and L-NMMA. Methods Twenty-nine healthy male subjects (age, 27 ± 1 years) were examined. In protocol 1 (N = 17), arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose arginine combined either with L-NMMA (total dose, 4.25 mg/kg; N = 9) or placebo (N = 8) were given. In protocol 2 (N = 12), L-NMMA was given before arginine infusion (100 mg/kg). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured at rest and at the end of each infusion step. Results In protocol 1, arginine dose dependently increased RPF and GFR (RPF: 599 ± 19 v 630 ± 18 v 690 ± 24 mL/min, P<.05; GFR: 111 ± 3 v 115 ± 3 v 121 ± 3 mL/min, P<.01; for baseline, arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could not be antagonized by coinfusion of L-NMMA to arginine 250 mg/kg: RPF and GFR remained unchanged in both the placebo and the L-NMMA group. In protocol 2, L-NMMA decreased RPF (492 ± 18 v 567 ± 27 mL/min, P<.01) and increased GFR (122 ± 4 v 118 ± 3 mL/min, P<.05). These changes could only be partially reversed by subsequent infusion of arginine (RPF: 533 ± 15 mL/min; GFR: 121 ± 4 mL/min; both parameters P = NS v L-NMMA and v baseline). Conclusions -arginine at a dose of 100 mg/kg is sufficient to analyze endothelial function of the renal vasculature. The prolonged effect of L-NMMA and arginine must be taken into account in study protocols using both substances. Thus, stimulation and blockade of NO synthase cannot be examined in the same protocol.