Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats.
We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca2+, Na+, K+, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [14C]nicardipine into the brains of five rats; the highest concentrations of [14C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na+ and K+ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca2+ accumulation more than it reduces Na+ and water accumulation and K+ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca2+ entry into ischemic cells.
Hadani
M
M
Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
Young
W
W
Flamm
E S
ES
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004573:Electrolytes / Q000378:metabolism*; D007477:Ions; D009529:Nicardipine / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004573:Electrolytes; D007477:Ions; D012964:Sodium; D009529:Nicardipine; D002118:Calcium