S. Ibayashi et al., Calcium antagonist isradipine reduces metabolic alterations in acute cerebral ischemia in spontaneously hypertensive rats, NEUROCHEM R, 25(3), 2000, pp. 349-355
The present study was designed to examine the effect of a calcium antagonis
t isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue
metabolism after 1-hour supratentorial ischemia induced by bilateral caroti
d artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, disso
lved in ethanol plus polyethylene glycol 400, diluted with saline to make t
he final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutan
eously either 30 min prior to BCL or just after the induction of incomplete
cerebral ischemia (n = 7 in each group). Vehicle injection was served as a
control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) an
d the cerebellar cortex (CeBF) was measured by hydrogen clearance technique
, and the supra- and infratentorial metabolites of the brain frozen in situ
were determined by the enzymatic method. Blood pressure was lowered, but C
BF was increased by PN administration in pre-BCL treatment study. After 1 h
our of BCL, CBF decreased to around 10% or less of the resting value, being
insignificant among the groups. Brain adenosine triphosphate was better pr
eserved in PN-administered groups. The increase in lactate level tended to
reduce dose dependently by PN treatment. PN also reduced the metabolic alte
rations in brain tissue with significance, even when administered just afte
r the induction of forebrain ischemia. It is considered that pre- as well a
s post-BCL administration of PN is beneficial to attenuate the metabolic al
terations in incomplete forebrain ischemia in SHR.