TY - JOUR
T1 - Participation of K+ channels in the endothelium-dependent and endothelium-independent components of the relaxant effect of rosuvastatin in rat aortic rings
AU - López, Jorge
AU - Mendoza, Roberto
AU - Cleva Villanueva, Guadalupe
AU - Martínez, Gustavo
AU - Castillo, Enrique F.
AU - Castillo, Carlos
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
KW - Aorta
KW - Endothelium-dependent relaxation
KW - Potassium channels
KW - Rosuvastatin
UR - http://www.scopus.com/inward/record.url?scp=49749126393&partnerID=8YFLogxK
U2 - 10.1177/1074248408321716
DO - 10.1177/1074248408321716
M3 - Artículo
SN - 1074-2484
VL - 13
SP - 207
EP - 213
JO - Journal of Cardiovascular Pharmacology and Therapeutics
JF - Journal of Cardiovascular Pharmacology and Therapeutics
IS - 3
ER -