Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine.
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.
Department of Nephrology and Hypertension (Room F03.226), University Medical Center, Heidelberglaan 100, P.O. Box 85500 3508 GA, Utrecht, The Netherlands.
Erwin
E
Blezer
Klaas
K
Nicolay
Roel
R
Goldschmeding
Hein
H
Koomans
Jaap
J
Joles
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
D000959:Antihypertensive Agents; D017311:Amlodipine