TY - JOUR
T1 - The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme a reductase-independent relaxant effect in rat aorta
AU - López-Canales, J. S.
AU - López-Sanchez, P.
AU - Perez-Alvarez, V. M.
AU - Wens-Flores, I.
AU - Polanco, A. C.
AU - Castillo-Henkel, E.
AU - Castillo-Henkel, C.
PY - 2011/5
Y1 - 2011/5
N2 - 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 synthase-2 (NOS-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 endotheliumindependent 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.
AB - 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 synthase-2 (NOS-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 endotheliumindependent 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.
KW - Endothelium-independent relaxation
KW - Nos-2
KW - Potassium channels
KW - Rat aorta
KW - Rosuvastatin methyl ester
UR - http://www.scopus.com/inward/record.url?scp=79958047607&partnerID=8YFLogxK
U2 - 10.1590/S0100-879X2011007500032
DO - 10.1590/S0100-879X2011007500032
M3 - Artículo
SN - 0100-879X
VL - 44
SP - 438
EP - 444
JO - Brazilian Journal of Medical and Biological Research
JF - Brazilian Journal of Medical and Biological Research
IS - 5
ER -