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.
Blezer
Erwin
E
Department of Nephrology and Hypertension (Room F03.226), University Medical Center, Heidelberglaan 100, P.O. Box 85500 3508 GA, Utrecht, The Netherlands.
Nicolay
Klaas
K
Goldschmeding
Roel
R
Koomans
Hein
H
Joles
Jaap
J
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