Background/Aims: Nicorandil, an ATP-sensitive potassium (KATP) channel opener, nitric oxide (NO) donor and antioxidant, was shown to exert a variety of pharmacological effects including cardioprotective properties. However, its mechanisms of action are not completely understood. The aims of this study were to examine whether nicorandil may alter angiotensin-II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Methods: Cultured rat cardiac fibroblasts were pretreated with nicorandil, then stimulated with Ang II, and cell proliferation and endothelin-1 (ET-1) expression were examined. The effects of nicorandil on Ang-II-induced reactive oxygen species (ROS) formation and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effects of nicorandil on NO production and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. Results: Nicorandil (0.1-10 μmol/l) caused a concentration- dependent inhibition of Ang-II-increased cell proliferation and ET-1 expression which were prevented by the KATP channel blocker glibenclamide (1 μmol/l). Nicorandil also inhibited Ang-II-increased ROS and ERK phosphorylation. In addition, nicorandil was found to increase the NO and eNOS phosphorylation. N-nitro-L-arginine methyl ester, an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of nicorandil on Ang-II-induced cell proliferation. Conclusion: Our results suggest that nicorandil prevents cardiac fibroblast proliferation, and the inhibitory effect might be associated with the opening KATP channels, by interfering with the generation of ROS, and the activation of the eNOS-NO pathway.

Original languageEnglish
Pages (from-to)144-151
Number of pages8
Issue number3-4
Publication statusPublished - Apr 2011


  • Angiotensin II
  • Cardiac fibroblast proliferation
  • Nicorandil
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology


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