Effects of perindopril on hypertension and stroke prevention in experimental animals.
BACKGROUND
Among the antihypertensive agents available for the treatment of hypertension, only angiotensin-converting enzyme (ACE) inhibitors have been shown to modify cardiovascular changes in structure and function.


OBJECTIVE
To study the effect of perindopril treatment on hypertension and stroke prevention in two genetic models of hypertensive rats.


METHODS
Adult (15 weeks old) spontaneously hypertensive rats (SHR) were treated with perindopril to determine the dose- and duration-dependent effects of treatment on systolic blood pressure, and the effect of withdrawal of this treatment on blood pressure and survival. In stroke-prone SHR, treatment was initiated in young animals (six weeks), and dose- and duration-dependent effects of perindopril treatment on stroke prevention were assessed.


RESULTS
In adult SHR, perindopril caused a dose-dependent lowering of blood pressure. Blood pressure was controlled for a 24 h period with a single daily dose. The magnitude of rebound hypertension after withdrawal of treatment was negatively correlated with duration of treatment. After 12 weeks of treatment, the blood pressure of treated SHR remained normotensive without further treatment, and the life span of treated SHR was also extended. Treatment of young, stroke-prone SHR with perindopril prevented stroke in these animals during the treatment period. After withdrawal of treatment, survival of the rats was increased in animals given a longer treatment period (24 weeks versus eight or 12 weeks).


CONCLUSIONS
Treatment with the ACE inhibitor perindopril is effective in the prevention of hypertension and stroke in experimental animals.
Department of Anaesthesia, McMaster University, Hamilton, Ontario.
R M
RM
Lee
H
H
Wang
J S
JS
Smeda
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D007211:Indoles; D020913:Perindopril