Assessment of endothelial function of the renal vasculature in human subjects

Am J Hypertens. 2002 Jan;15(1 Pt 1):3-9. doi: 10.1016/s0895-7061(01)02242-7.

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / administration & dosage
  • Blood Pressure / drug effects
  • Drug Interactions
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Enzyme Inhibitors / administration & dosage*
  • Glomerular Filtration Rate / drug effects
  • Heart Rate / drug effects
  • Humans
  • Kidney / blood supply*
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Renal Circulation / drug effects
  • Renal Circulation / physiology*
  • omega-N-Methylarginine / administration & dosage*

Substances

  • Enzyme Inhibitors
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III