Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Thomas P. Misko, William M. Moore, Thomas P. Kasten, G. Allen Nickols, John A. Corbett, Ronald G. Tilton, Michael L. McDaniel, Joseph R. Williamson, Mark G. Currie

Research output: Contribution to journalArticle

694 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalEuropean Journal of Pharmacology
Volume233
Issue number1
DOIs
StatePublished - Mar 16 1993

Keywords

  • Aminoguanidine
  • Nitric oxide synthase
  • Selective inhibitor inducible

ASJC Scopus subject areas

  • Pharmacology

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    Misko, T. P., Moore, W. M., Kasten, T. P., Nickols, G. A., Corbett, J. A., Tilton, R. G., McDaniel, M. L., Williamson, J. R., & Currie, M. G. (1993). Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. European Journal of Pharmacology, 233(1), 119-125. https://doi.org/10.1016/0014-2999(93)90357-N