Inhibition of cyclosporin-induced in vitro glomerular contraction by theophylline

Cyclosporin A (CsA) induces in vivo severe nephrotoxicity characterized by a large decrease in renal haemodynamics. The aim of this study is to show the ability of theophylline, a xanthic derivative, to diminish the CsA-induced vasoconstrictive effects by using two in vitro rat glomerular models, for example isolated glomeruli and cultured mesangial cells. Isolated glomeruli are obtained from the superficial renal cortex of male Sprague-Dawley rats by a sieving method. Mesangial cells are cultured in RPMI 1640 medium with 15% foetal calf serum (FCS). The area of either isolated glomeruli or mesangial cells is assessed by an image analyser with a video camera. Each glomerulus or mesangial cell serves as its own control by photographing them before any drug incubation and after incubation for 10, 20 and 30 min either in control solution or control solution with CsA or CsA and theophylline. CsA (10(-6)m) induces an important time-dependent decrease in the glomerular area (about 13.4% after 30 min). When theophylline is added only a slight decrease is noticed (about 3.4% after 30 min). The same results are obtained with mesangial cells. In conclusion, a direct vasoconstrictive effect of CsA in isolated glomeruli and mesangial cells can be confirmed. In addition, this effect can be partially prevented by theophylline.