Participation of K+ channels in the endothelium-dependent and endothelium-independent components of the relaxant effect of rosuvastatin in rat aortic rings.
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 Ca( 2+)-dependent K(+) channels of the slow subfamily.
López
Jorge
J
Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina, Col. Casco de Sto. Tomas, Mexico. skiold666@hotmail.com
Mendoza
Roberto
R
Cleva Villanueva
Guadalupe
G
Martínez
Gustavo
G
Castillo
Enrique F
EF
Castillo
Carlos
C
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D005464:Fluorobenzenes; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011453:Prostaglandins; D011743:Pyrimidines; D013449:Sulfonamides; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium; D019001:Nitric Oxide Synthase