Effects of K+Channel blockers on acetylcholine-induced vasodilation in guinea-pig choroid

The purpose of this study is to clarify which K+channels contribute to the acetylcholine (ACh)-induced vasodilation from the diameter changes in arterioles of the guinea-pig choroid. The choroid was isolated from the guinea-pig eyeball, pinned flat on a silicone rubber plate and superfused with warmed oxygenated (35 degrees C) Krebs solution. Diameters of choroidal arterioles were measured using video microscopy and a computer program for analysis. The effects of K+channel inhibitors (glibenclamide, tetraethylammonium [TEA], apamin and charybdotoxin [ChTX]) on the ACh-induced vasodilation were examined in arterioles which had been constricted by either norepinephrine (NE) or high K+solution. In NE (10(-5)m)-constricted arterioles, the combination of nitroarginine (10(-4)m) and indomethacin (10(-5)m) reduced ACh (10(-6)m)-induced vasodilatation by 24%. When high K+solution was used to constrict the arterioles, ACh-induced vasodilation was abolished by nitroarginine and indomethacin. In the presence of nitroarginine and indomethacin, the ACh-induced dilatation of NE-constricted arterioles was attenuated by TEA (10(-3)m), apamin (10(-7)m), and ChTX (10(-7)m) but not by glibenclamide (2x10(-5)m). Simultaneous application of apamin and ChTX inhibited the ACh (10(-6)m)-induced dilatation by 85%. In arterioles of guinea pig-choroid, nitric oxide and prostacyclin are not main mediators in ACh-induced vasodilation. Simultaneous activation of a set of Ca2+-sensitive K+channels may take most part of ACh-induced vasodilation.