Jpn. J. Pharmacol. 84 (1), 56-62 (2000)

Effects of Benidipine Hydrochloride on Cerebrovascular Lesions in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats: Evaluation by Magnetic Resonance Imaging

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 mg/kg daily for 7 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 mg/kg ameliorated neurological symptoms, significantly suppressing cerebrovascular damages on MRI. Benidipine at 3 mg/kg significantly decreased blood pressure for the first four 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© The Japanese Pharmacological Society 2000

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