Attenuation of ischemic and postischemic damage to brain metabolism and circulation by a novel Ca2+ channel antagonist, NC-1100, in spontaneously hypertensive rats.
We investigated the effect of a newly synthesized Ca2+ channel antagonist, NC-1100, on cerebral blood flow (CBF) and metabolism in spontaneously hypertensive rats. The rats received a bolus injection of 0.2 or 1.0 mg/kg NC-1100 i.v. and 1-h cerebral ischemia was then induced by bilateral carotid artery occlusion (group 1). The rats in group 2 were continuously infused with NC-1100 0.03 or 0.1 mg/kg per min, starting immediately after bilateral carotid artery occlusion, for the 1 h of ischemia and following 3-h recirculation. Group 1: during ischemia, CBF in all rats decreased to 6-8% of the resting values. At 1 h cerebral ischemia, brain tissue lactate increased 11.5-, 10.1- and 9.8-fold of the normal control given vehicle or NC-1100, 0.2 and 1.0 mg/kg, respectively. The ATP levels were better preserved by NC-1100 administration; 0.61 +/- 0.04 (mean +/- S.E.M.), 0.80 +/- 0.09 and 0.97 +/- 0.14 mmol/kg (P < 0.05 vs. vehicle), respectively. Group 2: during recirculation, CBF in NC-1100-treated rats returned to 83-90% of the resting values, but to only 65% in the vehicle group. Postischemic brain lactate at 3 h was less well preserved and ATP was dose dependently better preserved in NC-1100- than vehicle-treated rats. It is considered that pre- as well as postischemic administration of a Ca2+ channel antagonist, NC-1100, is beneficial to attenuate and also ameliorate the metabolic and circulatory derangement in the ischemic brain.
Sadoshima
S
S
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ibayashi
S
S
Nakane
H
H
Okada
Y
Y
Ooboshi
H
H
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D007773:Lactates; D010879:Piperazines; C050134:tamolarizine; D019344:Lactic Acid; D000255:Adenosine Triphosphate