The novel HMG-CoA reductase inhibitor, pitavastatin, induces a protective action in vascular endothelial cells through the production of nitric oxide (NO)

Abstract

This study sought to induce the effect of nitric oxide (NO) production in vascular endothelial cells by Pitavastatin, which is a novel HMG-CoA reductase inhibitor (statin). The growth capacity of vascular endothelial cells significantly (p<0.01) declined when stimulated with TNF-α (10 ng/ml). The growth capacity of the TNF-α treated cells recovered, when the TNF-α stimulation was performed after Pitavastatin (100 nM) pretreatment. The recovery of the growth capacity of the cells was suppressed by the presence of the NO synthase inhibitor, L-NAME. Pitavastatin increased NO production by the vascular endothelial cells in a dose and time dependent manner. The NO production was suppressed by the presence of mevalonic acid and geranylgeranyl pyrophosphate. In addition, the expression of endothelial nitric oxide synthase was strongly induced by Pitavastatin, and was suppressed by mevalonic acid and geranylgeranyl pyrophosphate by Western blot analysis. Our results show that Pitavastatin induces NO production by vascular endothelial cells, and protects vascular endothelial cells from injury due to the inflammatory reaction induced by TNF-α. © 2004 The Pharmaceutical Society of Japan.