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...
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| Format: | Article |
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Associação Brasileira de Divulgação Científica
2011-05-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000500009 |
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| author | J.S. López-Canales P. López-Sanchez V.M. Perez-Alvarez I. Wens-Flores A.C. Polanco E. Castillo-Henkel C. Castillo-Henkel |
| author_facet | J.S. López-Canales P. López-Sanchez V.M. Perez-Alvarez I. Wens-Flores A.C. Polanco E. Castillo-Henkel C. Castillo-Henkel |
| author_sort | J.S. López-Canales |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T23:05:12Z |
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| id | doaj.art-a57f237e42d649c9aff313614be19b45 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-10T23:05:12Z |
| publishDate | 2011-05-01 |
| publisher | Associação Brasileira de Divulgação Científica |
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| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-a57f237e42d649c9aff313614be19b452022-12-22T01:30:03ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2011-05-01445438444The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aortaJ.S. López-CanalesP. López-SanchezV.M. Perez-AlvarezI. Wens-FloresA.C. PolancoE. Castillo-HenkelC. Castillo-HenkelThe 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000500009Rat aortaRosuvastatin methyl esterEndothelium-independent relaxationPotassium channelsNOS-2 |
| spellingShingle | J.S. López-Canales P. López-Sanchez V.M. Perez-Alvarez I. Wens-Flores A.C. Polanco E. Castillo-Henkel C. Castillo-Henkel The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta Brazilian Journal of Medical and Biological Research Rat aorta Rosuvastatin methyl ester Endothelium-independent relaxation Potassium channels NOS-2 |
| title | The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta |
| title_full | The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta |
| title_fullStr | The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta |
| title_full_unstemmed | The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta |
| title_short | The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta |
| title_sort | methyl ester of rosuvastatin elicited an endothelium independent and 3 hydroxy 3 methylglutaryl coenzyme a reductase independent relaxant effect in rat aorta |
| topic | Rat aorta Rosuvastatin methyl ester Endothelium-independent relaxation Potassium channels NOS-2 |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000500009 |
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