Cyclosporine A induces endothelin-1 release from cultured rat vascular smooth muscle cells

Since vascular smooth muscle cells in culture are capable of secreting endothelin-1 (ET-1), we investigated the effect of cyclosporine A on ET-1 release from rat vascular smooth muscle cells. Cyclosporine A 10 microM significantly (P < 0.05) enhanced the secretion of ET-1 at 2, 8, 24 and 48 h (6.5 +/- 0.5, 11 +/- 0.7, 19 +/- 0.5, 37 +/- 1.6 fmol/10(6) cells, respectively) compared with vehicle (4.7 +/- 0.3, 8.1 +/- 0.6, 15 +/- 0.4, 27 +/- 2.0 fmol/10(6) cells, respectively). The cyclosporine-induced synthesis of ET-1 by vascular smooth muscle cell may participate in the pathogenesis of cyclosporine-induced vasoconstriction and vasculopathy via an autocrine regulatory mechanism.