Acute
cerebral ischemia was produced in rats by injection of
arachidonic acid (AA) into the internal carotid artery.
Evans blue (EB) was intravenously injected and its extravasation into the brain was determined as an
indicator of disturbances in the blood-brain barrier and endothelial cells. Control animals showed severe
cerebral edema and marked blue staining of the brain.
Benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content and the extravasation of EB. Similarly
nicardipine (100 micrograms/kg, i.p.) suppressed the elevation of water content and the extravasation of EB. Furthermore, both
benidipine (30 micrograms/kg, i.p.) and
nicardipine (100 micrograms/kg, i.p.) improved the neuronal
injuries following AA-injection. An
antiplatelet agent,
ticlopidine (100 mg/kg, i.p.), and a
thromboxane A2 synthetase inhibitor,
OKY-1581 (3 mg/kg, i.p.), also suppressed the elevation of cerebral water content. A
lipoxygenase inhibitor, AA-561 (200 mg/kg, p.o.), and a
cyclooxygenase inhibitor,
indomethacin (10 mg/kg, i.p.), did not prevent the increase in cerebral water content. Neither
benidipine (3-30 micrograms/kg, i.v.) nor
nicardipine (100 micrograms/kg, i.v.) inhibited the AgNO3-induced
thrombus formation of the abdominal aorta, whereas
ticlopidine (100 mg/kg, p.o.) and
OKY-1581 (3 mg/kg, i.v.) prevented the
thrombus formation. From the present results, it is suggested that
benidipine, as well as
nicardipine, may protect against AA-induced acute
cerebral infarction via a mechanism independent of antithrombotic action.