Mechanism of the relaxant effect of rosuvastatin lactone on rat aortic rings

Polanco Ponce Ana Cecilia, Perez Alvarez Victor Manuel, Wens Flores Isabel, Castillo Henkel Enrique, Lopez Sanchez Pedro, Lopez Canales Jorge Skiold, Castillo Hernandez Maria Del Carmen, Castillo Henkel Carlos

Research output: Contribution to journalArticlepeer-review

Abstract

The relaxant effect of the lactone of rosuvastatin was evaluated on aortic rings from male Wistar rats (250- 300 g) with and without endothelium, precontracted with 1.0 μM phenylephrine. The lactone presented a greater potency than rosuvastatin in relaxing aortic rings. Unlike rosuvastatin, the effect of its lactone was endotheliumindependent. Pretreatment with either indomethacin (10 microM) or mevalonate (1 mM) did not inhibit the relaxant effect of the lactone. L-NAME (10 microM), 1400 W (10 μM), or tetraethylammonium (TEA, 10 mM) partially inhibited the relaxant effect of the lactone on endothelium-denuded aortic rings. However, cycloheximide (10 μM) or the combination of TEA plus LNAME completely inhibited the relaxant effect. The NOS- 2 was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with lactone treated rings. In conclusion, rosuvastatin was associated with a relaxant effect dependent on both endothelium and HMG-CoA reductase in rat aorta, whereas the lactone exhibited an endothelium and HMG-CoA reductase-independent relaxant effect. Both nitric oxide produced by NOS-2 and K+ channels are involved in the relaxant effect of the lactone.

Original languageEnglish
Pages (from-to)1787-1794
Number of pages8
JournalFrontiers in Bioscience - Elite
Volume4 E
Issue number5
StatePublished - 1 Jan 2012

Keywords

  • Aorta
  • Endotheliumand HMG-CoA reductase-independent relaxation; Potassium channels; NOS-2
  • Rosuvastatin lactone

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