Cytoprotective effects of nitrates in a cellular model of hydronephrosis.
BACKGROUND
The earliest insult to the kidney following the onset of ureteral obstruction is a marked elevation in collecting system pressure. This imparts a mechanical stress that is transmitted directly from the collecting system to the kidney substance. Renal tubular injury is the principal functional and histological change encountered, with glomerular changes being less marked and occurring later. Nitric oxide (NO) has been shown to protect against renal injury in UO, but its mode of action has not been clearly defined.


METHODS
MDCK (canine) and HK-2 (human) renal tubular cells were grown under control conditions or subjected to mechanical strain for periods of 24 and 48 hours. Cells were studied treated with or without Fas-antibody, etoposide or diethyl maleate (DEM) alone or in combination with NG-monomethyl l-arginine (L-NMMA), sodium nitroprusside (SNP) or l-arginine. Cell proliferation and apoptosis was determined using propidium iodide DNA staining. NO production and inducible NO synthase (iNOS) expression were measured by the Griess reaction and Western blotting, respectively.


RESULTS
Cells subjected to mechanical strain displayed a decrease in the proportion of cells undergoing cell division. They also showed an increased susceptibility to apoptosis. Associated with this was a decrease in Bcl-2 expression. An increase in iNOS expression was seen in cells subjected to mechanical strain, but no increase in NO production. The cellular effects of mechanical strain were reversed by SNP and l-arginine.


CONCLUSIONS
Culture of renal tubule cells in an environment of mechanical strain results in an imbalance in homeostasis and a net cell loss. This can be reversed by the administration of an NO donor or precursor.
Hegarty
Nicholas J
NJ
Department of Surgery, Mater Misericordiae Hospital, University College Dublin, 47 Eccles Street, Dublin 7, Ireland.
Watson
R William G
RW
Young
Leonie S
LS
O'Neill
Amanda J
AJ
Brady
Hugh R
HR
Fitzpatrick
John M
JM
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D019610:Cytoprotection; D004285:Dogs; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D006869:Hydronephrosis / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008298:Maleates / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D013314:Stress, Mechanical; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008298:Maleates; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005047:Etoposide; C014476:diethyl maleate