Effects of an endogenous inhibitor of nitric oxide synthesis on postcapillary venules

Am J Physiol. 1995 Jun;268(6 Pt 2):H2224-31. doi: 10.1152/ajpheart.1995.268.6.H2224.


The objective of this study was to determine whether an inhibitor of nitric oxide (NO) synthase (NG,NG'-dimethyl-L-arginine; L-DMA) that is produced by vascular endothelium elicits the inflammatory responses induced by synthetic analogues of L-arginine such as NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration, leukocyte-platelet aggregation, and albumin leakage were monitored in rat mesenteric venules exposed to different concentrations of either L-DMA or L-NAME. Increases in leukocyte adherence (7- to 9-fold) and emigration (3- to 5-fold), platelet-leukocyte aggregation, mast cell degranulation, and an enhanced albumin leakage (30-50%) were observed within 30 min after exposing the microvascular bed to either inhibitor; however, leukocyte emigration and albumin leakage responded more intensely to L-NAME than to L-DMA. The microvascular alterations and mast cell degranulation were attenuated by addition of L-arginine to the superfusate. These results suggest that the L-DMA is capable of eliciting an inflammatory response at concentrations detected in plasma under certain pathological conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Blood Flow Velocity / drug effects
  • Blood Platelets / physiology
  • Cell Adhesion / drug effects
  • Cell Aggregation / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology*
  • Kinetics
  • Leukocytes / drug effects
  • Leukocytes / physiology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase
  • Rats
  • Rats, Sprague-Dawley
  • Splanchnic Circulation / drug effects
  • Splanchnic Circulation / physiology
  • Stereoisomerism
  • Venules / drug effects
  • Venules / physiology*


  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • NG-Nitroarginine Methyl Ester