Association of nitric oxide production and apoptosis in a model of experimental nephropathy.
BACKGROUND
In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR).


METHODS
The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis.


RESULTS
Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels.


CONCLUSIONS
We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.
Ozen
S
S
Department of Pediatric Nephrology and Rheumatology, Faculty of Pharmacy, University of Ankara, Turkey.
Usta
Y
Y
Sahin-Erdemli
I
I
Orhan
D
D
Gumusel
B
B
Yang
B
B
Gursoy
Y
Y
Tulunay
O
O
Dalkara
T
T
Bakkaloglu
A
A
El-Nahas
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004317:Doxorubicin / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006146:Guanidines; D010656:Phenylephrine; D009569:Nitric Oxide; D004317:Doxorubicin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine