Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
Volume 13, Issue 3, Pages 207-213Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1074248408321716
Keywords
aorta; rosuvastatin; endothelium-dependent relaxation; potassium channels
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Rosuvastatin was tested on rat aortic rings in the presence and absence of K+ channel blockers, mevalonic acid, and inhibitors of nitric oxide, prostaglandins, or endothelial-derived hyperpolarizing factor synthesis. The direct vascular effects of rosuvastatin were then evaluated by obtaining dose-response curves. Rosuvastatin relaxed aortic rings with and, to a lesser degree, without endothelium. Under both these conditions this effect was partially inhibited by L-NAME, tetraethylammonium, apamin + charybdotoxin (only administered together), or mevalonic acid. The combination of L-NAME with any of the other 3 treatments completely inhibited the effect of rosuvastatin, but indomethacin, clotrimazol, glibenclamide, charybdotoxin, or apamin alone had no effect. Therefore, the relaxation induced by rosuvastatin, even in the absence of endothelium, is partially related to 2 different mechanisms, one that is isoprenoid dependent and NO mediated and the other that is tied to the opening of Ca2+-dependent K+ channels of the slow subfamily.
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