PMID- 10540196
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20190513
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 118
IP  - 2
DP  - 1999 Nov
TI  - Induced nitric oxide (NO) synthesis in heterologous nephrotoxic nephritis; 
      effects of selective inhibition in neutrophil-dependent glomerulonephritis.
PG  - 309-14
AB  - Increased NO synthesis, due to inducible NO synthase (iNOS) activity, is found in 
      macrophage-associated glomerulonephritis. Little is known about NO in 
      neutrophil-dependent immune complex inflammation, and its role remains 
      controversial. We therefore studied early phase heterologous nephrotoxic 
      nephritis (HNTN) induced in rats by nephrotoxic globulin and the effects of 
      selective iNOS inhibition of this model. At 2 h of the model iNOS mRNA was 
      induced and nitrite (NO-2) was generated in glomeruli incubated ex vivo (5.2 +/- 
      1.0 nmol/2000 glomeruli per 24 h). There were 14.7 +/- 2.2 polymorphonuclear 
      neutrophils (PMN)/glomerulus (normal controls 0.1 +/- 0.1). At 8 h urinary 
      protein was 69 +/- 15.3 (normal controls 0. 6 +/- 0.2 mg/24 h). Peritoneal PMN 
      expressed iNOS and produced significant NO-2 (basal 11.2 +/- 0.3 nmol/106 cells 
      per 24 h). Selective iNOS inhibition with L-N6-(1-iminoethyl)-lysine (L-NIL) in 
      vitro inhibited nephritic glomerular and PMN NO-2 synthesis. In HNTN L-NIL in 
      vivo significantly suppressed elevated plasma NO-2/NO-3 levels (representative 
      experiment: 17 +/- 2 microM, untreated 40 +/- 4 microM, P = < 0.01, normal 
      control 18 +/- 2 microM). This inhibition did not affect leucocyte infiltration 
      into glomeruli or induce thrombosis. There was no consistent effect on 
      proteinuria. This is the first demonstration of glomerular iNOS induction and 
      high output NO production in the acute phase of PMN-dependent acute immune 
      complex glomerulonephritis. Selective iNOS inhibition does not affect the primary 
      mechanism of injury (leucocyte infiltration) in this model.
FAU - Waddington, S N
AU  - Waddington SN
AD  - Department of Histopathology, Imperial College School of Medicine at St Mary's, 
      London, UK.
FAU - Mosley, K
AU  - Mosley K
FAU - Cattell, V
AU  - Cattell V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heymann Nephritis Antigenic Complex)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (N(6)-(1-iminoethyl)lysine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Enzyme Induction/immunology
MH  - Enzyme Inhibitors/metabolism
MH  - Glomerulonephritis/chemically induced/enzymology/*immunology
MH  - Heymann Nephritis Antigenic Complex
MH  - Kidney Glomerulus/enzymology/immunology/pathology
MH  - Lysine/analogs & derivatives/pharmacology
MH  - Male
MH  - Membrane Glycoproteins/immunology
MH  - Neutrophils/enzymology/*immunology/metabolism
MH  - Nitric Oxide/*antagonists & inhibitors/*metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/biosynthesis
MH  - Nitric Oxide Synthase Type II
MH  - Rats
MH  - Rats, Inbred Lew
PMC - PMC1905410
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
PMCR- 2000/11/01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
PHST- 2000/11/01 00:00 [pmc-release]
AID - cei1049 [pii]
AID - 10.1046/j.1365-2249.1999.01049.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 1999 Nov;118(2):309-14. doi: 10.1046/j.1365-2249.1999.01049.x.