Actions of cyclosporin A on cultured rat mesangial cells.
The effects of cyclosporin A (CsA) on planar surface area of cultured rat mesangial cells (PCSA) and cross-sectional area of isolated rat glomeruli (GCSA) were tested. The same experiments were performed after preincubation with platelet activating factor (PAF) antagonists (BN 52021, alprazolam) or calcium channel blockers (verapamil). Areas of cells or glomeruli were analyzed by a computer-assisted method. CsA reduced PCSA in a time-dependent (significant effects began at 15 min, about 12% of reduction with 10(-6) M CsA) and dose-dependent (no effect at 10(-9) M CsA, maximal reduction of about 30% at 60 min of incubation with 10(-7) M CsA) fashion. BN 52021 (5.10(-5) M) and alprazolam (10(-5) M) completely inhibited the reduction of mesangial cell area induced by CsA. Verapamil (10(-5) M) only partially inhibited this action. Glomerular cross-sectional area decreased after 30 minutes of incubation with 10(-6) M CsA (1.45 +/- 0.02 vs. 1.55 +/- 0.02 m2.10(-8), P less than 0.001), an effect that was inhibited by BN 52021 or verapamil. In addition, 10(-6) M CsA increased PAF production by isolated rat glomeruli (425 +/- 80 pg/mg vs. 198 +/- 13 pg/mg in control glomeruli, P less than 0.01), an effect which was not inhibited by verapamil. These results suggest that CsA could reduce GFR by decreasing the glomerular ultrafiltration coefficient, perhaps as a consequence of the contraction of mesangial cells. PAF seems to play a pivotal role in the genesis of this action.
Rodríguez-Puyol
D
D
Department of Nephrology, Medical Research Institute, Fundación Jiménez Díaz, CSIC, Madrid, Spain.
Lamas
S
S
Olivera
A
A
López-Farré
A
A
Ortega
G
G
Hernando
L
L
López-Novoa
J M
JM
D000818:Animals; D002478:Cells, Cultured; D003524:Cyclosporins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats
D003524:Cyclosporins; D010972:Platelet Activating Factor