Glomeruli synthesize nitrite in experimental nephrotoxic nephritis.
Activated macrophages synthesize nitric oxide (NO) from L-arginine. In culture, the major stable end product is nitrite (NO2). Activated macrophages accumulate in glomeruli and are responsible for injury in experimental immune complex glomerulonephritis. We examined NO2- production by isolated glomeruli and urinary NO2- in accelerated nephrotoxic nephritis in the rat. Normal glomeruli did not produce NO2- spontaneously or when stimulated with lipopolysaccharide (LPS) (1 microgram/ml) or A23187 (2 microgram/ml). Cultured mesangial cells at first or seventh passage did not produce NO2- spontaneously or when stimulated. Nephritic glomeruli spontaneously produced NO2 at all times studied; this production was maximal at 24 hours after induction of glomerulonephritis (158.4 +/- 8.4 nmol/48 hr/ml, N = 3). The production of NO2- was inhibited 75 to 100% by NG-monomethyl-L-arginine (L-NMMA), and this inhibition was reversed by L-arginine, indicating NO2- production from L-arginine via NO. The production of NO2- was increased by LPS (1 microgram/ml) at 2, 7 and 21 days. NO2- was undetectable in normal rat urine; however, it was present in urine of rats with glomerulonephritis (Day 0 to 1:8161 +/- 2605 nmol/24 hr. N = 12). The production of NO in nephritic glomeruli may have implications for both the mechanism of glomerular injury and glomerular hemodynamics.
Cattell
V
V
Department of Histopathology, St. Mary's Hospital Medical School, Paddington, London, United Kingdom.
Cook
T
T
Moncada
S
S
D000818:Animals; D002478:Cells, Cultured; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew
D009573:Nitrites