Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol 1993 Mar 16;233(1):119-25
Date
03/16/1993Pubmed ID
7682510DOI
10.1016/0014-2999(93)90357-nScopus ID
2-s2.0-0027402115 (requires institutional sign-in at Scopus site) 715 CitationsAbstract
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.
Author List
Misko TP, Moore WM, Kasten TP, Nickols GA, Corbett JA, Tilton RG, McDaniel ML, Williamson JR, Currie MGAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid OxidoreductasesAnimals
Aorta, Thoracic
Arginine
Cells, Cultured
Citrulline
Cyclic GMP
Guanidines
Macrophages
Male
Muscle, Smooth, Vascular
Nitric Oxide
Nitric Oxide Synthase
Nitrites
Rats
Rats, Sprague-Dawley
Spectrometry, Fluorescence
