PREVENTION OF STROKE WITH PERINDOPRIL TREATMENT IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: To determine the protective effects of perindopril treatmen t in the prevention of stroke and the relation between preventive effe cts and the histopathology of the brain and kidneys in male stroke-pro ne spontaneously hypertensive rats (SHRSP). Design: Prospective animal study. Interventions: Beginning at 6 weeks of age, SHRSP were treated with either distilled water (control) or perindopril for different pe riods (8, 12 or 24 weeks) and at different dosages (1 or 4 mg/kg per d ay). Outcome measures: Regular determination of systolic blood pressur e, heart rate and body weight until death; at necropsy, macroscopic an d microscopic examinations of the brain and kidneys. Results: Control SHRSP developed severe hypertension (up to 250 mm Hg) by 11 weeks of a ge and died of stroke within 14 weeks of age. Treatment with perindopr il (4 mg/kg per day for 8 or 12 weeks or either 1 or 4 mg/kg per day f or 24 weeks) attenuated the blood pressure rise and prevented stroke. In untreated SHRSP, the last blood pressure measurement before the fir st stroke sign was significantly higher than in SHRSP of the same age treated with perindopril. Withdrawal of the treatment resulted in a ri se in blood pressure in all the treatment groups, to approximately 260 mm Hg within 4 weeks. Most of the rats treated for 8 or 12 weeks died within 10 weeks after withdrawal of treatment, whereas those treated for 24 weeks survived up to 43 weeks of age. Treatment also prevented damage to the brain and kidneys and reduced the severity of lesions in the brain and kidneys after treatment withdrawal. Conclusion: Treatme nt of SHRSP with perindopril prevents stroke through the suppression o f blood pressure rise and prevention of tissue damage in the brain and the kidneys. Longer treatment decreased the rate of mortality due to stroke after the withdrawal of treatment as well as the severity of le sions in the brain and kidneys.