MitoK(ATP) opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat.
We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 microl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 +/- 0.7, n = 13) compared with sham treatment (9.5 +/- 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 +/- 3.6% (n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 +/- 4.8% (n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 microl saline), a selective blocker of mitoK(ATP) channels (n = 6). These results indicate that selective opening of the mitoK(ATP) channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA. KATSUYOSHIS@aol.com
Katsuyoshi
K
Shimizu
Zsombor
Z
Lacza
Nishadi
N
Rajapakse
Takashi
T
Horiguchi
James
J
Snipes
David W
DW
Busija
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry; D015221:Potassium Channels; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D008565:Membrane Proteins; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D003981:Diazoxide