Details

Autor(en) / Beteiligte

• Reilly, Christopher M.
• Farrelly, Libby W.
• Viti, Dana
• Redmond, Shakisha T.
• Hutchison, Florence
• Ruiz, Phil
• Manning, Pam
• Connor, Jane
• Gilkeson, Gary S.

Titel

Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of inducible nitric oxide synthase

Ist Teil von

• Kidney international, 2002-03, Vol.61 (3), p.839-846

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2002

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Modulation of renal disease in MRL/ lpr mice by pharmacologic inhibition of inducible nitric oxide synthase. MRL-MPJFaslpr (MRL/lpr) mice spontaneously develop lupus-like disease characterized by immune complex glomerulonephritis and overproduction of nitric oxide (NO). Blocking NO production pharmacologically by a non-specific nitric oxide synthase (NOS) inhibitor ameliorated renal disease in MRL/lpr mice while genetically deficient inducible NOS (iNOS) mice developed proliferative glomerulonephritis similar to wild-type controls. To clarify the role of iNOS in the pathogenesis of nephritis in MRL/lpr mice, we treated mice with two different NOS inhibitors. Either NG-monomethyl-L-arginine (L-NMMA), a nonspecific NOS inhibitor, or L-N6-(1-iminoethyl)lysine (L-NIL), an iNOS specific inhibitor, was administered in the drinking water from 10 through 22 weeks of age with disease progression monitored over time. Control mice received water alone. Both L-NMMA and L-NIL blocked NO production effectively in MRL/lpr mice. As expected, neither L-NNMA nor L-NIL had an effect on antibody production, immune complex deposition or complement activation. Although both NOS inhibitors decreased protein excretion, L-NMMA was more effective than L-NIL. Pathologic renal disease was significantly decreased at 19 weeks in both treatment groups. At 22 weeks the L-NIL treated mice, but not the L-NMMA mice, had significantly reduced renal disease scores compared to controls. These results indicate that specific inhibition of iNOS blocks the development of pathologic renal disease in MRL/lpr mice.