Suppression of nitric oxide production by cyclosporin A and FK506A in rat vascular smooth muscle cells.

1. The effects of the immunosuppressants cyclosporin A (CsA) and FK506 on nitric oxide (NO) synthesis induced by lipopolysaccharide (LPS) or cytokines were examined in rat vascular smooth muscle cells (VSMC) in culture. 2. CsA inhibited by up to 90% the accumulation of nitrite induced by LPS, but FK506 had a weaker effect on nitrite accumulation induced by LPS in these cells. Both CsA and FK506 (at 1 mumol/L) significantly inhibited nitrite production induced by recombinant murine interleukin-1 beta (rIL-1 beta). 3. Given their differing potency, it is likely that CsA and FK506 suppress induction of NO synthase through different intracellular mechanisms. This action could contribute to the side effects of CsA therapy.