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Glomeruli synthesize nitrite in experimental nephrotoxic nephritis
1Department of Histopathology, St. Mary's Hospital Medical School, Paddington, London, United Kingdom.
Kidney International
|December 1, 1990
Summary
Activated macrophages produce nitric oxide (NO), measured as nitrite (NO2-), in glomerulonephritis. This NO2- production in nephritic glomeruli suggests a role in kidney injury and blood flow regulation.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Activated macrophages are implicated in immune complex glomerulonephritis.
- Macrophages synthesize nitric oxide (NO) from L-arginine, with nitrite (NO2-) as a stable end product.
- Glomerular macrophages contribute to kidney injury.
Purpose of the Study:
- To investigate nitric oxide (NO2-) production in isolated glomeruli and urine during experimental immune complex glomerulonephritis.
- To determine the source and regulation of NO2- production in nephritic glomeruli.
Main Methods:
- Isolated glomeruli and urine from rats with accelerated nephrotoxic nephritis were analyzed for NO2- production.
- Inhibition studies using NG-monomethyl-L-arginine (L-NMMA) and L-arginine were performed.
- Lipopolysaccharide (LPS) stimulation was used to assess NO2- production.
Main Results:
- Nephritic glomeruli exhibited spontaneous NO2- production, peaking at 24 hours post-induction.
- NO2- production was significantly inhibited by L-NMMA and restored by L-arginine, confirming NO synthesis from L-arginine.
- Urinary NO2- levels were elevated in rats with glomerulonephritis compared to normal controls.
- LPS stimulation increased NO2- production in nephritic glomeruli at various time points.
Conclusions:
- Activated macrophages in glomeruli produce nitric oxide (NO) during immune complex glomerulonephritis.
- NO production in nephritic glomeruli may play a role in the pathogenesis of glomerular injury and affect glomerular hemodynamics.