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

• Published in: Frontiers in bioscience (Elite edition) Vol. 4; no. 5; p. 1787
• Main Authors: Ana Cecilia, Polanco-Ponce, Victor Manuel, Perez-Alvarez, Isabel, Wens-Flores, Enrique, Castillo-Henkel, Pedro, Lopez-Sanchez, Jorge Skiold, Lopez-Canales, Maria del Carmen, Castillo-Hernandez, Carlos, Castillo-Henkel
• Format: Journal Article
• Language: English
• Published: Singapore 01-01-2012
• Subjects: Animals; Aorta - drug effects; Aorta - enzymology; Aorta - physiology; Hydroxymethylglutaryl CoA Reductases - metabolism; Imines - pharmacology; In Vitro Techniques; Indomethacin - pharmacology; Lactones - pharmacology; Male; Muscle Relaxation - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase Type II - metabolism; Phenylephrine - pharmacology; Potassium Channels - physiology; Rats; Rats, Wistar; Sulfonamides - pharmacology
• ISSN: 1945-0508
• DOI: 10.2741/e499

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 microM phenylephrine. The lactone presented a greater potency than rosuvastatin in relaxing aortic rings. Unlike rosuvastatin, the effect of its lactone was endothelium-independent. 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 microM), or tetraethylammonium (TEA, 10 mM) partially inhibited the relaxant effect of the lactone on endothelium-denuded aortic rings. However, cycloheximide (10 microM) or the combination of TEA plus L-NAME 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.