Cyclosporine A Stimulates Endothelin Release

Administration of cyclosporine A is often associated with the development of renal dysfunction and hypertension. Because recent data provide evidence that endothelin (ET) might be involved in mediating cyclosporine-associated cardiovascular and renal side effects, the present study aimed to investigate the influence of cyclosporine A on ET release from cultured smooth-muscle cells and whether ET plasma concentrations are elevated in cyclosporine-treated patients. Addition of cyclosporine A to the medium of cultured human smooth-muscle cells, isolated from atherosclerotic iliac arteries, induced a dose-dependent increase in ET release. ET plasma levels were significantly elevated in cyclosporine-treated patients after bone marrow transplantation, compared to control groups. These data suggest that enhanced ET release might be involved in mediating the cyclosporine-associated side effects.