Prevention of stroke with perindopril treatment in stroke-prone spontaneously hypertensive rats.
OBJECTIVE
To determine the protective effects of perindopril treatment in the prevention of stroke and the relation between preventive effects and the histopathology of the brain and kidneys in male stroke-prone spontaneously hypertensive rats (SHRSP).


METHODS
Prospective animal study.


METHODS
Beginning at 6 weeks of age, SHRSP were treated with either distilled water (control) or perindopril for different periods (8, 12 or 24 weeks) and at different dosages (1 or 4 mg/kg per day).


METHODS
Regular determination of systolic blood pressure, heart rate and body weight until death; at necropsy, macroscopic and microscopic examinations of the brain and kidneys.


RESULTS
Control SHRSP developed severe hypertension (up to 250 mm Hg) by 11 weeks of age and died of stroke within 14 weeks of age. Treatment with perindopril (4 mg/kg per day for 8 or 12 weeks or either 1 or 4 mg/kg per day for 24 weeks) attenuated the blood pressure rise and prevented stroke. In untreated SHRSP, the last blood pressure measurement before the first stroke sign was significantly higher than in SHRSP of the same age treated with perindopril. Withdrawal of the treatment resulted in a rise 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.


CONCLUSIONS
Treatment of SHRSP with perindopril prevents stroke through the suppression of 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 lesions in the brain and kidneys.
Wang
H
H
Smooth Muscle Research Programme, Faculty of Health Sciences, McMaster University, Hamilton, Ont.
Delaney
K H
KH
Kwiecien
J M
JM
Smeda
J S
JS
Lee
R M
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate; D006973:Hypertension / Q000517:prevention & control; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020913:Perindopril; D011446:Prospective Studies; D051381:Rats; D011918:Rats, Inbred SHR; D015996:Survival Rate; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D020913:Perindopril