Cyclosporin A generates superoxide in smooth muscle cells.
Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier studies have demonstrated that the increase in the vasopressin type 1 receptor induced in vascular smooth muscle cells in the presence of CsA is probably due to superoxide (Krauskopf et al., J Biol Chem 278, 41685-41690, 2003). This increase in vasopressin receptor is likely at the base of increased vascular responsiveness to vasoconstrictor hormones and hypertension induced by CsA. Here, we demonstrate that CsA produces superoxide. In addition, our data show that superoxide generation does not originate from the major cellular superoxide generating systems NAD(P)H oxidase or xanthine oxidase. Our results suggest that the side effects of CsA could be diminished with the help of SOD mimetic drugs.
Krauskopf
Alexandra
A
Laboratory of Pharmacology, Geneva-Lausanne School of pharmacy, University if Geneva, Geneva 1205, Switzerland
Lhote
Philippe
P
Petermann
Olivier
O
Ruegg
Urs T
UT
Buetler
Timo M
TM
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004996:Ethidium / Q000031:analogs & derivatives; D005452:Fluoresceins; D016166:Free Radical Scavengers / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics; D013481:Superoxides / Q000378:metabolism*
D005452:Fluoresceins; D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; C067883:dihydroethidium; D013481:Superoxides; C029569:diacetyldichlorofluorescein; D016572:Cyclosporine; D013482:Superoxide Dismutase; D004996:Ethidium