Hypertension, Vol 23, 659-666, Copyright © 1994 by American Heart Association
NK Thybo, N Korsgaard, S Eriksen, KL Christensen and MJ Mulvany
Long-term treatment of young spontaneously hypertensive rats (SHR) with
angiotensin-converting enzyme (ACE) inhibitors has a persistent effect on
blood pressure when treatment is withdrawn. The aim of the present study
was to determine whether this effect could be mediated by the effect of
treatment on resistance-artery structure. We determined the dose dependence
of ACE-inhibitor therapy on blood pressure and small- artery structure
during treatment and on the recovery of blood pressure when treatment was
withdrawn. SHR (40 per group) were treated from age 4 to 24 weeks with one
of three doses of perindopril (0.4, 0.8, or 1.5 mg/kg per day). Control
groups were untreated SHR and Wistar-Kyoto rats. At 24 weeks, treatment was
stopped and small arteries were taken from half of the rats from the
mesenteric, femoral, cerebral, and coronary vascular beds for morphological
and functional measurements. The blood pressure of the other half of the
rats was followed until 36 weeks of age. During treatment, perindopril
caused a dose-dependent reduction in blood pressure and in the media-lumen
ratio and media area of the small arteries, whereas there was a
dose-dependent increase in lumen diameter. The effect of treatment on the
structure of arteries from the different vascular beds was homogeneous.
Compared with values from Wistar-Kyoto rats, blood pressure normalization
in SHR was not associated with full normalization of structure. After
withdrawal of treatment, there was an inverse relation between perindopril
dose and the persistent effect.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Dose-dependent effects of perindopril on blood pressure and small- artery structure
Department of Pharmacology, University of Aarhus, Denmark.
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