Hideyuki Funato (1), Hiroyuki Kawano (1), Yasushige Akada (1), Yukio
Katsuki (1), Masami Sato (1) and Akio Uemura (2)
(1) Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd.,
722 Jinba-aza-Uenohara, Gotemba 412, Japan
(2) Biosciences Research Laboratory, Mochida Pharmaceutical Co., Ltd., 1-1-1
Kamiya, Kita-ku, Tokyo 115, Japan
Abstract: We investigated the effects of lacidipine on focal
cerebral ischemia in rats, and these effects were compared with those of
nicardipine. Drugs were administered orally 5 min after middle cerebral
artery occlusion (MCAO). Neurological scores as described by Bederson et
al. (Stroke 17, 472-476, 1986) and cerebral infarct size (CIS) determined
by the 2,3,5-triphenyltetrazolium chloride staining method were measured
24 hr after MCAO. Cerebral blood flow (CBF) and energy metabolites were
determined by the hydrogen clearance method and an enzymatic method, respectively.
In the drug-untreated group, we observed low-CBF of approximate 13 ml/100
g/min during 0.5 - 6 hr of occlusion and extensive cerebral infarction associated
with severe neurologic deficits (ND). Lacidipine at 1 and 3 mg/kg, although
it lowered blood pressure, improved low-CBF to approximate 20 ml/100 g/min
during 1.5 -6 hr of occlusion and increased tissue levels of ATP 6 hr after
MCAO in a dose-dependent manner. Nicardipine at 30 mg/kg also improved low-CBF
and increased tissue levels of ATP significantly. However, the improvement
of low-CBF by nicardipine was transient. Lacidipine at 3 mg/kg reduced CIS
and ameliorated ND significantly. In contrast, nicardipine at 30 mg/kg could
not ameliorate ND in spite of a significant reduction of CIS similar to
that of lacidipine (3 mg/kg). These results suggest that the improvement
of focal cerebral ischemia by lacidipine may be partly due to long-lasting
improvement of collateral blood supply to the ischemic area.
Keywords: Lacidipine, Calcium antagonist, Focal cerebral ischemia, Cerebral
blood flow, Energy metabolism