Nitric oxide (NO) donor 3-morpholinosydnonimine antagonizes cyclosporin A-induced contraction in two in vitro glomerular models

M. Potier, J. Winicki, J. Cambar
Cell Biol Toxicol. 1996-12-01; 12(4-6): 335-339
DOI: 10.1007/bf00438167

PubMed

1. Cell Biol Toxicol. 1996 Dec;12(4-6):335-9. doi: 10.1007/BF00438167.

Nitric oxide (NO) donor 3-morpholinosydnonimine antagonizes cyclosporin
A-induced contraction in two in vitro glomerular models.

Potier M(1), Winicki J, Cambar J.

Author information:
(1)Laboratoire de Biologie Cellulaire, UFR des Sciences Pharmaceutiques,
Bordeaux, France.

Cyclosporin A induces in vivo a severe nephrotoxicity characterized by a large
decrease in renal hemodynamics. The aim of this study is to establish the
ability of the known NO donor 3-morpholinosydnonimine (SIN-1) to prevent the
cyclosporin A-induced contraction by using rat isolated glomeruli and cultured
glomerular mesangial cells. Isolated rat glomeruli are obtained from the renal
superficial cortex by a sieving method. Mesangial cells are cultured in RPMI
1640 with 15% fetal calf serum. The planar surface area (PSA) of either isolated
glomeruli or mesangial cells is assessed using an image analyzer. Each
glomerulus or mesangial cell serves as its own control through calculation of
the area before any drug incubation and after incubation for 10, 20 and 30 min
either in control solution or in control solution with cyclosporin A alone or
cyclosporin A and SIN-1. Cyclosporin A (10(-6) mol/L) induces an important
time-dependent contraction of either glomerulus or mesangial cell. When
pretreated with different concentrations of SIN-1 (10(-4) to 10(-9) mol/L), only
a slight size decrease is noted. In conclusion, a direct constrictive effect of
cyclosporin A in isolated glomeruli and mesangial cells can be prevented by the
NO donor SIN-1, suggesting an important involvement of the nitric oxide pathway
in the cyclosporin A-induced nephrotoxicity.