Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Eur J Pharmacol. 1993 Mar 16;233(1):119-25. doi: 10.1016/0014-2999(93)90357-n.


Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell, and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

Publication types

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

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Amino Acid Oxidoreductases / biosynthesis
  • Animals
  • Aorta, Thoracic / drug effects
  • Arginine / metabolism
  • Cells, Cultured
  • Citrulline / metabolism
  • Cyclic GMP / biosynthesis
  • Guanidines / pharmacology*
  • Macrophages / enzymology
  • Male
  • Muscle, Smooth, Vascular / enzymology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase
  • Nitrites / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Fluorescence


  • Guanidines
  • Nitrites
  • Citrulline
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Cyclic GMP
  • pimagedine