Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase.

J Neuroimmunol. 1996 Feb;64(2):123-33. Unique Identifier : AIDSLINE MED/96182330
Zhao W; Tilton RG; Corbett JA; McDaniel ML; Misko TP; Williamson JR; Cross AH; Hickey WF; Department of Pathology, Dartmouth Medical School,; Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756 USA.

Abstract: This study assessed the role of de novo nitric oxide (NO) production in the pathogenesis of experimental allergic encephalomyelitis (EAE) by using aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS), which preferentially inhibits the cytokine- and endotoxin-inducible isoform of NOS versus the constitutive isoforms consisting of endothelial and neuronal NOS. The maximum clinical severity of EAE and the duration of illness were significantly reduced or totally inhibited by twice daily subcutaneous injection of 100 mg/kg body weight AG. Histochemical staining for NADPH diaphorase, which detects enzymatic activity of NOS, revealed positive reactivity in untreated EAE rats both in parenchymal blood vessel walls and in anterior horn cell neurons, while normal rats and rats with EAE treated with AG showed predominantly the neuronal positivity. Moreover, this NADPH staining pattern was further supported by the immunohistochemical findings that endothelial NOS (eNOS) expression was increased in blood vessels in the inflamed lesions of untreated EAE rats and that inducible NOS (iNOS) was detected in some inflammatory cells, while treatment with AG could significantly reduce both iNOS and eNOS production. These results suggest that: (i) both iNOS and eNOS are upregulated in inflamed areas of the rat central nervous system in EAE; (ii) increased NO production plays a role in the development of clinical signs in EAE; and (iii) selective inhibitors of iNOS and/or eNOS may have therapeutic potential for the treatment of certain autoimmune diseases.

Keywords: Animal Biological Markers/ANALYSIS CD4-CD8 Ratio/DRUG EFFECTS Encephalomyelitis, Allergic/PATHOLOGY/PREVENTION & CONTROL/ *PHYSIOPATHOLOGY Enzyme Inhibitors/*PHARMACOLOGY/THERAPEUTIC USE Female Guanidines/*PHARMACOLOGY/THERAPEUTIC USE Immunohistochemistry Nitric-Oxide Synthase/*ANTAGONISTS & INHIB/METABOLISM NADPH Dehydrogenase/METABOLISM Rats Rats, Inbred Lew Spinal Cord/CHEMISTRY/PATHOLOGY/PHYSIOPATHOLOGY Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
960930
M9690909

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .