Assessment of endothelial function of the renal vasculature in human subjects.
BACKGROUND
L-Arginine, the substrate of nitric oxide (NO) synthase, and N(G)-monomethyl-L-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 L-arginine to be used and the duration of action of L-arginine and L-NMMA.


METHODS
Twenty-nine healthy male subjects (age, 27+/-1 years) were examined. In protocol 1 (N = 17), L-arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose L-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 L-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, L-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, L-arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could not be antagonized by coinfusion of L-NMMA to L-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 L-arginine (RPF: 533+/-15 mL/min; GFR: 121+/-4 mL/min; both parameters P = NS v L-NMMA and v baseline).


CONCLUSIONS
L-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 L-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.
Delles
Christian
C
Department of Medicine/Nephrology, University of Erlangen-Nürnberg, Germany.
Jacobi
Johannes
J
Schlaich
Markus P
MP
John
Stefan
S
Schmieder
Roland E
RE
D000328:Adult; D001120:Arginine / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III