Nicorandil attenuates cyclic strain-induced endothelin-1 expression through the inhibition of reactive oxygen species formation and the enhancement of nitric oxide production in human umbilical vein endothelial cells

Ju Chi Liu, Chien Sung Tsai, Jin Jer Chen, Tzu-Hurng Cheng

Research output: Contribution to journalArticle

Abstract

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, induces vasodilation, blood pressure decrease and cardioprotection. However, the intracellular mechanism of nicorandil remains to be delineated. The aims of this study were to test the hypothesis that nicorandil may alter strain-induced endothelin-1 (ET-1) secretion and nitric oxide (NO) production, and to identify the putative underlying signaling pathways in human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were exposed to cyclic strain in the presence of nicorandil, ET-1 expression was examined by reverse transcriptase-polymerase chain reaction and ELISA. Activation of extracellular signal-regulated protein kinase (ERK) and endothelial nitric oxide synthase (eNOS) were assessed by Western blot analysis. We show that nicorandil inhibits strain-induced ET-1 expression. Nicorandil also inhibits strain-increased reactive oxygen species (ROS) formation and ERK phosphorylation. On the contrary, NO production and eNOS phosphorylation were enhanced by nicorandil treatment in HUVECs. Furthermore, L-NAME, an inhibitor of NO synthase, and the siRNA transfection for eNOS partially attenuated the inhibitory effect of nicorandil on strain-induced ET-1 expression. We demonstrate for the first time that nicorandil inhibits strain-induced ET-1 secretion via the suppression of ROS production and the enhancement of strain-increased NO production in HUVECs. This study delivers important new insight in the molecular pathways that may contribute to the beneficial effects of nicorandil in the cardiovascular system.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalTherapeutic Research
Volume31
Issue number3
Publication statusPublished - 2010

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Keywords

  • Cyclic strain
  • Endothelin-1
  • Nicorandil
  • Nitric oxide

ASJC Scopus subject areas

  • Medicine(all)

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