Antihypertensive effects of perindopril treatment in adult spontaneously hypertensive rats.
OBJECTIVE
To determine the effect of perindopril treatment and treatment withdrawal in the prevention of hypertension in adult male spontaneously hypertensive rats (SHR).


METHODS
Beginning at 15 weeks of age, male SHR were treated with either distilled water (control) or different daily dosages of perindopril (1, 2 or 4 mg/kg) by gavage for 10 weeks, followed by 10 weeks of treatment withdrawal. Systolic blood pressure, heart rate and body weight of adult SHR were determined at regular intervals before, during and after the treatment withdrawal periods. At the end of the treatment withdrawal period, plasma and tissue samples were taken for measurement of noradrenaline levels. Angiotensin-converting enzyme (ACE) activity in the plasma from adult SHR and Wistar-kyoto (WKY) rats treated with perindopril 4 mg/kg for two weeks was measured by a radioassay method 6 and 24 h after treatment.


RESULTS
Treatment with perindopril caused a dose-dependent lowering of blood pressure in SHR during the 10-week treatment. After withdrawal of the treatment, persistent lowering of blood pressure was found in SHR treated with higher dosages (2 or 4 mg/kg), but not in the 1 mg/kg group. There was no difference in the tissue level of noradrenaline among the control group and SHR previously treated with perindopril. In SHR and WKY treated with perindopril for two weeks, plasma level of ACE activity was reduced longer than 24 h compared with their respective controls.


CONCLUSIONS
Chronic treatment of adult SHR with perindopril has a dose-dependent effect on the blood pressure of these animals both during and after withdrawal of treatment, but such a treatment had no long term effects on the noradrenaline levels in various tissues.
Lee
R M
RM
Department of Anaesthesia, Faculty of Health Sciences, McMaster University, Hamilton, Ontario. rmkwlee@fhs.mcmaster.ca
Lu
M
M
Gillies
L
L
Werstiuk
E S
ES
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000517:prevention & control*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine; D020913:Perindopril