Hideo Ueno, Takuji Hara, Akio Ishi and Katsuichi Shuto
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 2458
Fujimagari, Ube, Yamaguchi 755-8501, Japan
Abstract: We determined possible protective effects of benidipine
hydrochloride (benidipine), a dihydropyridine calcium antagonist, on cerebrovascular
lesions in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP).
The animals were orally treated with benidipine at 1, 3 and 10ﾊmg/kg daily
for 7ﾊweeks, and their neurological symptoms, body weight changes, systolic
blood pressure and cerebrovascular lesions on magnetic resonance imaging
(MRI) were determined at various time points of treatment. Moreover, the
brains of the rats that showed cerebrovascular lesions on MRI in the course
of treatment or completed 7-week treatment were examined histopathologically.
Control rats presented such symptoms as sedation, ataxia and aggressiveness,
while their MRI analysis revealed high signals over wide areas from the
occipital to frontal cortex and from the corpus callosum to external capsule.
These high signal areas corresponded in location to edematous or softening
lesions revealed by the histopathological observation. Treatment with benidipine
at 3 and 10ﾊmg/kg ameliorated neurological symptoms, significantly suppressing
cerebrovascular damages on MRI. Benidipine at 3ﾊmg/kg significantly decreased
blood pressure for the first fourﾊweeks but it did not thereafter. These
findings demonstrate that benidipine can protect salt-loaded SHRSP from
cerebrovascular injury as assessed by MRI.
Keywords: Benidipine, Calcium channel blocker, Magnetic resonance imaging,
Stroke-prone spontaneously hypertensive rat, Cerebrovascular lesion
Copyrightｩ The Japanese Pharmacological Society 2000
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