Stroke-prone spontaneously hypertensive rats (SHRSPs) are vulnerable to
ischemia and delayed neuronal death (DND) of hippocampus pyramidal cells when bilateral carotid arteries are occluded for only 10 min. Since this occlusion induces just mild
ischemia, the resulting DND may be an appropriate animal model for
dementia in patient with
essential hypertension exposed to small ischemic insults. This study was designed to compare the effects of the
antihypertensive drugs lercanidipine,
nicardipine,
lisinopril,
valsartan, and
hydralazine on occlusion-induced DND in SHRSPs. Drugs were administered for 2 weeks, from 15 to 17 weeks of age. 0.1%
Nicardipine and 0.01 or 0.03%
lercanidipine were administered in the SP diet (about 61.3, 5.7, and 18.8 mg/kg/day, respectively), and the remaining drugs were administered
at 10 mg/kg/day using the mini-osmotic pump. The animals were operated on at 16 weeks of age, and DND was analyzed by histological examination 1 week later. Systolic blood pressure was measured at 15, 16, and 17 weeks of age. For chronic treatment,
Calcium-channel blockers were administered from 8 to 17 weeks of age. All
antihypertensive drugs significantly lowered systolic blood pressure at 16 weeks of age.
Hydralazine and
lisinopril were associated with the greatest reduction; however,
lercanidipine,
nicardipine, and
valsartan effectively reduced systolic blood pressure to within a medium range. DND was significantly inhibited only by 0.03%
lercanidipine. Chronic treatment with 0.03%
lercanidipine also protected pyramidal neurons. The results of this study demonstrate that the long-acting, lipophilic
Calcium-channel blocker lercanidipine inhibits occlusion-induced DND in SHRSPs and that
lercanidipine may effectively reduce
dementia induced by small ischemic insults in patients with
essential hypertension.