The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta

the relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 μm phenylephrine. the methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log ic50 values of -6.88 and -6.07 m, respectively. unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. pretreatment with 10 μm indomethacin did not inhibit, and pretreatment with 1 mm mevalonate only modestly inhibited the relaxant effect of the methyl ester. nω-nitro-l-arginine methyl ester (l-name, 10 μm), the selective nitric oxide-2 (no-2) inhibitor 1400 w (10 μm), tetraethylammonium (tea, 10 mm), and cycloheximide (10 μm) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. however, the combination of tea plus either l-name or cycloheximide completely inhibited the relaxant effect. inducible no synthase (nos-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. in conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme a reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme a reductase-dependent relaxant effect. both no produced by nos-2 and k+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.