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.
Takeda
Y
Y
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Itoh
Y
Y
Yoneda
T
T
Miyamori
I
I
Takeda
R
R
D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D016232:Endothelins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D016232:Endothelins; D016572:Cyclosporine