Pimobendan inhibits the activation of transcription factor NF-kappa B - A mechanism which explains its inhibition of cytokine production and inducible nitric oxide synthase

Pimobendan, an inhibitor of phosphodiesterase III with calcium sensitizing properties, inhibits the production of cytokines and nitric oxide. In the p resent study, the effects of pimobendan and other inotropic agents on the a ctivation of transcription factor NF-kappa B were examined. Pimobendan sign ificantly decreased the expression of luciferase protein in A549 cells tran sfected with the NF-kappa B reporter plasmid, stimulated with interleukin ( LL)-1 beta, tumor necrosis factor-alpha, or phorbol 12-myristate 13 acetate . However, high concentrations of amrinone, vesnarinone, or NKH 477 decreas ed promoter activity only slightly. Electrophoretic mobility shift assay al so showed inhibition of NF-kappa B activation by pimobendan. Pimobendan pos sesses the unique property of inhibiting NF-kappa B, which may be independe nt of phosphodiesterase inhibition. (C) 2000 Elsevier Science Inc. All righ ts reserved.