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

Eur J Pharmacol. 2002 May 24;444(1-2):75-81. doi: 10.1016/s0014-2999(02)01609-6.

Abstract

Dihydropyridine Ca(2+) 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 Ca(2+) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amlodipine / therapeutic use*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Brain Edema / drug therapy
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Stroke / etiology
  • Stroke / prevention & control*

Substances

  • Antihypertensive Agents
  • Amlodipine