The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta
| Autor: | A.C. Polanco, E.F. Castillo-Henkel, C. Castillo-Henkel, Jorge Skiold López-Canales, Víctor Pérez-Álvarez, Pedro López-Sánchez, I. Wens-Flores |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Physiology Vasodilator Agents Nitric Oxide Synthase Type II Reductase Pharmacology Biochemistry chemistry.chemical_compound General Pharmacology Toxicology and Pharmaceutics Cycloheximide Rosuvastatin Calcium lcsh:QH301-705.5 Aorta Sulfonamides lcsh:R5-920 General Neuroscience Tetraethylammonium General Medicine Hydroxymethylglutaryl-CoA reductase Rosuvastatin methyl ester Vasodilation NOS-2 NG-Nitroarginine Methyl Ester cardiovascular system lcsh:Medicine (General) medicine.drug Coenzyme A Immunology Biophysics Rat aorta Potassium channels medicine.artery medicine Animals Rosuvastatin Rats Wistar Phenylephrine Cell Biology Rats Fluorobenzenes Pyrimidines chemistry lcsh:Biology (General) Endothelium-independent relaxation Hydroxymethylglutaryl CoA Reductases Endothelium Vascular |
| Zdroj: | Brazilian Journal of Medical and Biological Research v.44 n.5 2011 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC Brazilian Journal of Medical and Biological Research, Vol 44, Iss 5, Pp 438-444 (2011) Brazilian Journal of Medical and Biological Research, Volume: 44, Issue: 5, Pages: 438-444, Published: MAY 2011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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