Demonstration of direct vasoconstrictive effect of cyclosporin on glomeruli isolated from human kidney

: Cyclosporin (CsA), a potent immunosuppressive agent, can induce severe renal damage, characterized by lesions in the tubulo interstitial region and decreased renal function. Isolated glomeruli can be considered as a fruitful model to evidence the direct effect of drugs at the level of glomerular structures. The present study aims to evidence, in this model, vasoactive response of isolated human renal glomeruli induced by different CsA concentrations. Area changes of such isolated glomeruli can be assessed by a semi-automatic morphometric method, using a video-camera device coupled with a microprocessor (Biocom 2000). Experiments are done under double bind conditions. CsA-induced decrease in glomeruli area is dose- and time-dependent. CsA effect is rapid in that glomerular area is significantly decreased even after 5 min. incubation; vasoconstrictive effect is more important (and maximum) after 10 min. incubation; significant decrease can be noted with 10(-7) M (-11.41%) and 10(-6) M (-10.26%). In conclusion, the isolated glomerulus model allows us to demonstrate the direct vasoconstrictive effect of CsA, that can in part explain the renal functional changes and the acute renal failure often described in human clinic.