EFFECTS OF BARNIDIPINE HYDROCHLORIDE, A CALCIUM ANTAGONIST, ON ATHEROSCLEROSIS IN CHOLESTEROL-FED RABBITS

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The effects of barnidipine hydrochloride, a new calcium antagonist, on the development of atherosclerosis were evaluated in cholesterol-fed rabbits. Two groups of twelve rabbits received l or 3mg/kg of barnidipine hydrochloride orally daily for 10 weeks. Another 12 rabbits received 12mg/kg/day of nifedipine, 6mg/kg twice a day, for 10 weeks as a positive control. These animals were fed 1% cholesterol diet, 100g daily during the treatment period. Twelve cholesterol-fed animals served as a cholesterol control group. Over the 10-week period, serum cholesterol levels were significantly elevated in all groups, but there were no difference among these groups. After 10-week treatment, the aortas were removed and opened longitudinally. Sclerotic areas on the intimal surface were determined by planimetry. The ratios of sclerotic foci were significantly suppressed in the groups of barnidipine hydrochloride 3mg/kg and nifedipine 12mg/kg. Cholesterol contents in the arterial wall of aortic arch and abdominal portion in animals given barnidipine hydrochloride were significantly decreased in a dose dependent manner. The heart was cut into three transverse sections, and subepicardial and intramyocardial coronary arteries were examined microscopically. These examinations revealed no difference between the groups given bar-nidipine hydrochloride or nifedipine and cholesterol control group in the incidence and degree of sclerotic changes. From these data, it is concluded that barnidipine hydrochloride suppresses the development of atherosclerosis and the cholesterol contents in aortic wall without reduction of serum cholesterol levels in cholesterol-fed rabbits. Also, histopathological examination revealed no effects on the cardiac coronary arteries as in other calcium antagonists such as lanthanum, diltiazem, and flunarizine.
日本毒性病理学会の論文
1995-03-01

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