Hideyuki Funato (1), Mitsutoshi Watanabe (2) and Akio Uemura (3)
(1) Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd.,
722 Jinba-aza-Uenohara, Gotemba 412-8524, Japan
(2) Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., 342 Gensuke,
Fujieda 426-8640, Japan
(3) Biosciences Research Laboratory, Mochida Pharmaceutical Co., Ltd., 1-1-1
Kamiya, Kita-ku, Tokyo 115-8515, Japan
Abstract: The aim of this study was to investigate the therapeutic
effectiveness of lacidipine in stroke-prone spontaneously hypertensive rat
(SHRSP) with cerebrovascular lesions in comparison with nicardipine. SHRSP
were fed 1% saline as drinking water. After the onset of stroke, saline
was replaced with water and each drug was administered orally once a day
for 3 weeks. In the drug-untreated group, recurrence of
stroke was repeated, deterioration and amelioration of neurological deficits
(ND) were repeated, and histological examination and measurement of regional
blood flow (rBF) using nonradioactive colored microspheres performed at
the end of treatment revealed severe damages and significantly decreased
rBF in brain and kidney, respectively. In kidney, not only lacidipine (1
mg/kg) but also nicardipine (30 mg/kg)
decreased vascular lesions and ameliorated low-rBF significantly. Both drugs
also inhibited the recurrence of stroke completely even at a low dose that
did not ameliorate severe hypertension. Neuronal damages and
ND in each lacidipine-treated group were ameliorated significantly, whereas
those in each nicardipine-treated group were slightly improved. Lacidipine
at 1 mg/kg alone ameliorated the cerebral low-rBF significantly even at
24 hr after administration. These results suggest that a long-lasting improvement
of low-rBF after stroke may be useful in the treatment of SHRSP with cerebrovascular
lesions.
Keywords: Lacidipine, Calcium antagonist, Vascular lesion, Regional blood
flow, Stroke-prone spontaneously hypertensive rat (SHRSP)