| Co-Investigator(Kenkyū-buntansha) |
OGURA Yuuichirou Nagoya city university, medical school, professor, 医学部, 教授 (70191963)
OZEKI Hironori Nagoya city university, medical school, assistant professor, 医学部, 講師 (60254299)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The purpose of this study is to clarify which endothelium-derived vasodilators and K+ channels contribute to the vasodilation in arterioles of the guinea-pig choroids. Experiment1 was done on acetylcholine (ACh)-induced vasodilation. The choroid was isolated from the guinea-pig eyeball, pinned flat on a silicone plate, and superfused with Kerbs solution. Diameters of choroidal arterioles were measured using video microscopy. In norepinephrine (NE, 1-5M)-constricted arterioles, the combination of nitroarginine(N-Arg, 10-4M) and indomethacin (Indo, 10-5M) reduced ACh (10-6M)-induced vasodilation by 24%. When high K+ solution was used to constrct the arterioles, ACh-induced vasodilation was abolished by N-Arg and Ind. In the presence of N-Arg and Ind, the ACh-induced dilation of NE-constricted arterioles was attenuated by tetraethylammonium(10-3M), apamin(10-7M) and charybdotoxin(ChTX, 10-7M) but not by glibenclamide(Glib, 2'10-5M). Simultaneous application of apamin and ChTX inhibited th
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e ACh-induced dilation by 85%. In arterioles of guinea-pig choroids, 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. Experiment 2 was performed on NaCN-induced ischemic vasodilation. The guinea-pig choroid was prepared in the same way as experiment 1. Vasodilatory effects were examined after the choroid was exposed to glucose-free/NaCN solution solution for 10 minutes. N-Arg, Glib, and ChTX significantly inhibited glucose-free/NaCN-induced vasodilation by 47%, 62%, and 24%, respectively. No significant inhibitory effect was observed with Indo. Simultaneous application of Glib and ChTX reduced vasodilation by 77%. When Glib and ChTX were added together to N-Arg, dilation was reduced by 86%. With high K+ Krebs solution, ischemia caused a slight vasodilation(11%), which was significantly inhibited by N-Arg. Glucose-free/NaCN-induced ischemic vasodilation was mainly mediated by NO and KATP channels. A part of NO-mediated vasodilation was induced independent of the opening of K+ channels. Less
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