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 arte rioles of the guinea-pig choroid. The choroid was isolated from the guinea-pig eyeball, pinned flat on a sili cone rubber plate and superfused with warmed oxygenated (35 degrees C) Kreb s solution. Diameters of choroidal arterioles were measured using video mic roscopy and a computer program for analysis. The effects of K+ channel inhi bitors (glibenclamide, tetraethylammonium [TEA], apamin and charybdotoxin [ ChTX]) on the ACh-induced vasodilation were examined in arterioles which ha d 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 vasodila tation by 24%. When high K+ solution was used to constrict the arterioles, ACh-induced vasodilation was abolished by nitroarginine and indomethacin. I n the presence of nitroarginine and indomethacin, the ACh-induced dilatatio n of NE-constricted arterioles was attenuated by TEA (10(-3) M), apamin (10 (-7) M), and ChTX (10(-7) M) but not by glibenclamide (2 x 10(-5) M). Simul taneous 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 se t of Ca2+-sensitive K+ channels may take most part of ACh-induced vasodilat ion. (C) 1999 Academic Press.