Hypertension, Vol 16, 603-614, Copyright © 1990 by American Heart Association
SB Harrap, WM Van der Merwe, SA Griffin, F Macpherson and AF Lever
Our study examines the long-term cardiovascular effects after a brief
period of angiotensin converting enzyme (ACE) inhibitor treatment in young
spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3
mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of
age. Systolic blood pressure was measured in the tail weekly until 25 weeks
of age. Corresponding control groups received distilled water for the same
periods. In each treatment group blood pressure was reduced significantly
during treatment, rose when treatment stopped, but plateaued significantly
below control SHR thereafter. This difference in blood pressure at 25 weeks
of age was due to reduced total peripheral resistance as determined by
microsphere methods, but plasma renin activity and angiotensin II
concentrations were not different. Cardiac hypertrophy was also reduced in
treated SHR. In a separate experiment, perindopril treatment from 6 to 10
weeks of age resulted in a significant reduction in the media/lumen ratios
of mesenteric resistance vessels at 32 weeks of age. Concomitant
administration of angiotensin II with perindopril from 6 to 10 weeks of age
not only prevented the long-term effects on blood pressure seen with
perindopril treatment alone but was associated with cardiovascular
hypertrophy in excess of untreated control SHR. Finally, perindopril given
for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had
no significant long-term effects on blood pressure. These results
demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is
sufficient to prevent the full expression of genetic hypertension and
cardiovascular hypertrophy and that angiotensin II might be important in
the development of hypertension in this model, its role in later life being
less important.
ARTICLES
Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term
MRC Blood Pressure Unit, Western Infirmary, Glasgow, Scotland, UK.
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