Potassium channel opener reduces extracellular glutamate concentration in rat focal cerebral ischemia.
The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.
Fujita
H
H
Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan.
Takizawa
S
S
Nanri
K
K
Matsushima
K
K
Ogawa
S
S
Shinohara
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D018698:Glutamic Acid; C074338:Y 26763