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.
Tamai
K
K
Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan.
Suzuki
H
H
Hashitani
H
H
Shirai
S
S
Ogura
Y
Y
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002829:Choroid / Q000098:blood supply*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D011464:Epoprostenol; D000109:Acetylcholine; D007213:Indomethacin