Effect of late modulation of nitric oxide production on murine lupus.
MRL/MpJ-Faslpr (MRL-lpr) and New Zealand Black/ White (NZB/W) mice develop spontaneous autoimmune disease characterized by autoantibody production and glomerulonephritis that progresses in parallel with increasing systemic nitric oxide (NO) production. A previously published study from our laboratory indicated that oral administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (NMMA) before the onset of clinical disease significantly decreased renal and joint pathology in MRL-lpr mice. To characterize the effect of late modulation of NO production in murine SLE, we administered oral NMMA and/or restricted dietary arginine after disease onset in two murine models of SLE. When receiving combined NMMA and arginine restriction, MRL-lpr mice had reduced joint pathology scores and NZB/W mice had lower renal pathology scores than control mice. These results indicate that modulating NO production after the onset of disease diminishes disease severity in two models of SLE, although not as effectively as treating before disease onset.
Oates
J C
JC
Medical Research Service, Ralph H. Johnson VAMC, Charleston, South Carolina, USA.
Ruiz
P
P
Alexander
A
A
Pippen
A M
AM
Gilkeson
G S
GS
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000517:prevention & control; D004277:DNA, Single-Stranded / Q000276:immunology; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011507:Proteinuria / Q000188:drug therapy; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase