Forefronts In Nephrology: Nitric Oxide And Inflammation
Kidney International (2002) 61, 834–838; doi:10.1046/j.1523-1755.2002.00229.x
Selective inhibition of inducible nitric oxide synthase enhances intraglomerular coagulation in chronic anti-Thy 1 nephritis
Ralf Westenfeld, Alexander Gawlik, Emile De Heer, Masashi Kitahara, Faikah Abou-Rebyeh, Juergen Floege and Markus Ketteler
Department of Medicine II, University Hospital Aachen, Aachen, and Department of Nephrology, Hannover Medical School, Hannover, Germany; and Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Correspondence: Ralf Westenfeld, M.D., Department of Medicine II, University Hospital Aachen, Pauwelsstra
e 30, D-52057 Aachen, Germany. E-mail: Ralf.Westenfeld@rwth-aachen.de
Abstract
Selective inhibition of inducible nitric oxide inhibition enhances intraglomerular coagulation in chronic anti-Thy 1 nephritis.
Background
A particular Lewis rat substrain (LEW/Maa) develops chronic glomerulonephritis in the anti-Thy 1 model (aThy 1-GN) characterized by increased microaneurysm formation, chronic glomerular sclerosis and persistent albuminuria. This phenotype is accompanied by increased and prolonged glomerular induction of inducible nitric oxide synthase (iNOS) when compared to the LEW/Moe substrain, in which aThy 1-GN resolves quickly. We investigated the effect of selective iNOS inhibition by L-N6-(1-iminoethyl)-lysine (L-NIL) administration on aThy 1-GN in LEW/Maa rats.
Methods
Nephritic rats were studied over a period of 7 days. L-NIL–treated animals received 20 mg/day L-NIL in the drinking water starting two days prior to disease induction. iNOS activity was determined in cultured glomeruli and in urine samples, respectively. Severity of aThy 1-GN was determined by scoring glomerular matrix expansion and microaneurysm formation, and by albuminuria measurements (ELISA). Immunohistochemical evaluation was performed including staining for macrophages (ED-1), platelets (PL-1) and fibrin deposition.
Results
L-NIL treated rats (+NIL) showed a significant decrease in peak nitrate production by ex vivo cultured glomeruli, and in urinary nitrate excretion versus untreated nephritic rats (-NIL). Mean arterial pressure remained unchanged in both +NIL and -NIL rats. +NIL rats developed significantly increased albuminuria (+44%) associated with a significant increase in glomerular platelet (+45%) and fibrin deposition (+48%).
Conclusions
Selective inhibition of iNOS aggravated albuminuria in chronic aThy 1-GN in LEW/Maa rats. Induction of iNOS during the inflammatory phase of this model may be a partially protective mechanism by interfering with intraglomerular coagulation processes.
Keywords:
platelets, L-NIL, glomerulonephritis, fibrin, mesangioproliferative glomerulonephritis, renoprotection
