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Abstract
We examined the antioxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), on superoxide anion formation activated by angiotensin II (Ang II) in vitro. The effects of fluvastatin were also compared to simvastatin and a water-soluble analog of alpha-tocopherol, trolox. Treatment of human aortic smooth muscle cells (hASMC) with Ang II for 24 hours resulted in a 3.2 +/- 0.5-fold increase in intracellular superoxide anion formation as detected by lucigenin assay. hASMC treated with clinical concentrations of fluvastatin (0-100 nM) showed a dose-dependent decrease in Ang II-activated superoxide anion formation. The addition of similar concentrations of trolox to hASMC inhibited Ang II-activated superoxide anion formation in a dose-dependent manner. However, simvastatin at similar doses failed to inhibit Ang II-activated superoxide anion formation by hASMC. Our results indicate that in addition to its hypocholesterolemic effect, fluvastatin may have direct antioxidative effects, suggesting its possible protective effect on atherosclerotic process.