ANTIHYPERTENSIVE EFFECTS OF PERINDOPRIL TREATMENT IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS

OBJECTIVE: To determine the effect of perindopril treatment and treatm ent withdrawal in the prevention of hypertension in adult male spontan eously hypertensive rats (SHR). ANIMALS AND METHODS: Beginning at 15 w eeks of age, male SHR were treated with either distilled water (contro l) or different daily dosages of perindopril (1, 2 or 4 mg/kg) by gava ge for 10 weeks, followed by 10 weeks of treatment withdrawal. Systoli c blood pressure, heart rate and body weight of adult SHR were determi ned at regular intervals before, during and after the treatment withdr awal periods. At the end of the treatment withdrawal period, plasma an d tissue samples were taken for measurement of noradrenaline levels. A ngiotensin-converting enzyme (ACE) activity in the plasma from adult S HR and Wistar-Kyoto (WKY) rats treated with perindopril 4 mg/kg for tw o 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 withdraw al of the treatment, persistent lowering of blood pressure was found i n 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 respect ive controls. CONCLUSIONS: Chronic treatment of adult SHR with perindo pril has a dose-dependent effect on the blood pressure of these animal s both during and after withdrawal of treatment, but such a treatment had no long term effects on the noradrenaline levers in various tissue s.