title: 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-alpha (10 ng/ml). The growth capacity of the TNF-alpha treated cells recovered, when the TNF-alpha 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-alpha.
authors.affiliation: Clinical Laboratory Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokoro
authors.forename: Juyong
authors.initials: J
authors.lastname: Wang
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011106:Polyisoprenyl Phosphates; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C108475:pitavastatin; C002963:geranylgeranyl pyrophosphate; D008798:Mevalonic Acid; D019331:NG-Nitroarginine Methyl Ester