Here, we show that nicorandil attenuates MCT-induced endothelial damage and apoptosis in pulmonary vasculature under PAH through production of endothelial NO synthase (eNOS) and anti-apoptotic factors; the production is mediated by the cell survival signaling cascades, phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) pathways, which are mainly activated via the opening of KATP channels. This evidence concerns the gene NOS3 and pulmonary arterial hypertension.