%0 Journal Article %A Glaucia E. Callera %A Alvaro Yogi %A Rita C. Tostes %A Luciana V. Rossoni %A Lusiane M. Bendhack %T Ca2+-Activated K+ Channels Underlying the Impaired Acetylcholine-Induced Vasodilation in 2K-1C Hypertensive Rats %D 2004 %R 10.1124/jpet.103.062810 %J Journal of Pharmacology and Experimental Therapeutics %P 1036-1042 %V 309 %N 3 %X We tested the hypothesis that an abnormal function of K+ channels in vascular smooth muscle cells plays a key role in the impaired acetylcholine (ACh) vasodilation in aortas from two kidney-one clip (2K-1C) hypertensive rats and further investigated the K+ channel subtype involved in this altered response. ACh-induced endothelium-dependent relaxation was assessed in aortic rings from 2K-1C and normotensive two kidney (2K) rats. Glibenclamide, an ATP-sensitive K+ channel blocker, did not inhibit ACh-induced relaxation in aortic rings from 2K or 2K-1C rats. The voltage-dependent K+ channels inhibitor 4-aminopyridine attenuated ACh-induced relaxation in both groups. Charybdotoxin and iberiotoxin, blockers of Ca2+-sensitive (KCa) and large-conductance KCa (BKCa) channels, respectively, reduced ACh-induced relaxation in aortic rings from 2K rats without affecting this response in those from 2K-1C rats, abolishing the differences between groups. ACh-induced relaxation in vessels from both 2K and 2K-1C rats was unaffected by apamin, a small-conductance KCa blocker. NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one], an activator of KCa, induced a smaller vasodilation in endothelium-denuded aortic rings from 2K-1C rats compared with those from 2K rats. Iberiotoxin reduced sodium nitroprusside-induced relaxation in endothelium-denuded aortic rings from 2K without affecting this response in those from 2K-1C rats. The inhibition of Na+,K+-ATPase with ouabain had no effects on ACh-induced relaxation in aortic rings from 2K-1C or 2K rats. These data indicate that a deficient functional activity of BKCa channels plays a key role in the impaired ACh vasodilation in aortas from 2K-1C rats. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/309/3/1036.full.pdf