Administration of nitric oxide synthase inhibitors in experimental autoimmune neuritis and experimental autoimmune encephalomyelitis.
The nitric oxide (NO) synthase pathway is activated during experimental autoimmune inflammation of the central nervous system, and administration of aminoguanidine, an inhibitor of the cytokine-inducible NO synthase (NOS), ameliorated the disease course of autoimmune encephalomyelitis in the SJL mouse. We studied the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune neuritis (EAN) and experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. NG-L-monomethyl-arginine (L-NMMA), a competitive inhibitor of NOS, partially suppressed T cell line-mediated EAN, but not myelin-induced EAN, myelin basic protein (MBP)-induced EAE, or T cell line-mediated EAE. Aminoguanidine (AG), a selective inhibitor of the cytokine-inducible NOS, enhanced MBP-induced EAE, but had no significant effects on myelin-induced EAN. Two other NOS inhibitors, nitro-arginine methyl-ester and N-nitro arginine, had only little or no effects in EAN and EAE. The administration of NOS inhibitors showed some striking effects in EAN and EAE, but the observed diversity of actions points to a much more complex role of the NO pathway than previously suggested.
Zielasek
J
J
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Jung
S
S
Gold
R
R
Liew
F Y
FY
Toyka
K V
KV
Hartung
H P
HP
D000085:Acetates / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D019331:NG-Nitroarginine Methyl Ester; D009444:Neuritis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D011917:Rats, Inbred Lew; D019323:omega-N-Methylarginine
D000085:Acetates; D006146:Guanidines; D004676:Myelin Basic Protein; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C018824:ammonium acetate; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester