Jpn. J. Pharmacol. 80 (3), 199-208 (1999)


Therapeutic Effects of a Calcium Antagonist, Lacidipine,
on Stroke-Prone Spontaneously Hypertensive Rats With Cerebrovascular Lesions

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)


Copyrightę The Japanese Pharmacological Society 1999

[Back to TOC]