| 14978190 |
Callera GE, Yogi A, Tostes RC, Rossoni LV, Bendhack LM: Ca2+-activated K+ channels underlying the impaired acetylcholine-induced vasodilation in 2K-1C hypertensive rats. J Pharmacol Exp Ther. 2004 Jun;309(3):1036-42. Epub 2004 Feb 20.
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 Ca (2+)-sensitive (K (Ca)) and large-conductance K (Ca) (BK (Ca)) 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 K (Ca) blocker. NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-2 H-benzimidazol-2-one], an activator of K (Ca), 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 BK (Ca) channels plays a key role in the impaired ACh vasodilation in aortas from 2K-1C rats. |
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