An ATP-sensitive potassium channel activator reduces infarct volume in focal cerebral ischemia in rats.
ATP-sensitive potassium channels are activated under hypoxic or ischemic conditions. The effects of ATP-sensitive potassium channel activators on cerebrovasculature and cerebral blood flow (CBF) are not well understood. We examined the effect of the ATP-sensitive potassium channel activator Y-26763 on focal cerebral ischemia in rats. In 24 spontaneously hypertensive rats, either Y-26763 (24 micrograms/kg) or vehicle was given by intracarotid infusion over 60 min, starting 30 min before photochemically induced thrombotic occlusion of the middle cerebral artery. CBF was measured by laser-Doppler flowmetry in the peri-ischemic penumbral cortex. Although Y-26763 lowered systemic blood pressure by 13 mmHg, the infarct volume assessed 3 days after the occlusion was significantly smaller in the Y-26763-treated group (n = 12, 71.2 +/- 22.0 mm3) than in the control group (n = 12, 94.7 +/- 20.4 mm3, P = 0.013). Y-26763 did not affect CBF before or after occlusion compared with CBF values of the control group. The results are consistent with the view that the activation of the ATP-sensitive potassium channel is neuroprotective in focal cerebral ischemia.
Takaba
H
H
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nagao
T
T
Yao
H
H
Kitazono
T
T
Ibayashi
S
S
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D001578:Benzopyrans; D015221:Potassium Channels; D000255:Adenosine Triphosphate; C074338:Y 26763