Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine

Dihydropyridine Ca2+ channel antagonists, initiated together with high salt intake, prevent the development of hypertension and subsequent cerebral damage in stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the dihydropyridine Ca2+ channel antagonist amlodipine (approximately 15 mg/kg/day) could also reverse established hypertension and cerebral damage. SHRSP drank 1% NaCl from 8 weeks of age. Cerebral damage (cerebral edema and blood-brain barrier integrity) was investigated with magnetic resonance imaging twice a week. Systolic blood pressure was measured weekly. All rats developed severe hypertension and subsequent cerebral damage (defined as day 0). Untreated controls (n=7) died at day 12 (range: 7-28). Oral treatment with amlodipine(n=7), initiated at day 0, reduced systolic blood pressure, reversed cerebral edema and restored blood-brain barrier integrity. Systolic blood pressure remained low and eventually rats died after 450 days (range: 350-580) showing nephrosis but no recurrence of cerebral damage. In conclusion, established hypertension and cerebral damage are reversed by amlodipine in SHRSP. (C) 2002 Elsevier Science B.V All rights reserved.