CYCLOSPORINE-A-INDUCED CONTRACTION OF ISOLATED RAT AORTIC SMOOTH-MUSCLE CELLS

The mechanisms by which the immunosuppressive drug cyclosporine A (CsA ) induces hypertension and nephrotoxicity are still not fully understo od. Although smooth muscle cell (SMC) contraction is probably the mech anism of vasoconstriction, the direct contractive effect of CsA on SMC s has not yet been demonstrated. Thus, it was the purpose of this stud y to evaluate the direct effects of CsA in cultured SMCs through inter active image analysis. In aortic SMCs, CsA at the concentrations of 0. 01, 0.1 and 1 mu M, caused a concentration-dependent decrease of the p lanar cross-sectional area (PCSA) after 30 min and 60 min of treatment . The PCSA decreases were statistically significantly different from c ontrol at all concentrations. No cytotoxicity was observed under these conditions. Ten minutes preincubation of SMCs with a monoclonal antib ody against endothelin-l (ET-1) significantly prevented the CsA effect s at 1 mu M When the same antibody was heat inactivated or an unspecif ic antibody (anti-desmin immunoglobulin G) was applied, the CsA-induce d contractions were not affected. These data suggest that CsA can caus e a direct contractive effect on vascular SMCs. This effect is partly mediated by ET-1. (C) 1997 Elsevier Science Inc.