Hypertension, Vol 14, 645-651, Copyright © 1989 by American Heart Association
JP Clozel, H Kuhn and F Hefti
Chronic hypertension is associated with a lower cerebral vascular reserve
due to thickening of the media of cerebral vessels. The goal of the present
study was to determine if long-term inhibition of angiotensin converting
enzyme with cilazapril, a new long-acting angiotensin converting enzyme
inhibitor, could improve cerebral vascular reserve. For this purpose, two
groups of 12 spontaneously hypertensive rats were compared. One group was
treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and
was compared with a group treated with placebo. A third group of 12
Wistar-Kyoto rats treated with placebo was used as reference. At the end of
the treatment period, cerebral vascular reserve was evaluated by measuring
cerebral blood flow (radioactive microspheres) at rest and during maximal
vasodilation induced by seizures provoked by bicuculline. Then, the rats
were perfusion-fixed, and morphometry of the cerebral vasculature was
performed. Cerebral vascular reserve was severely impaired in the
spontaneously hypertensive rats since their maximal cerebral blood flow was
decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized
cerebral blood flow reserve. This normalization was associated with a
decreased thickness of the medial layer in the carotid artery, the middle
cerebral artery, and in the pial arteries larger than 100 microns. Further
studies are required to determine whether this decreased medial thickness
is due to the normalization of blood pressure induced by cilazapril or to
the reduction of trophic factors such as angiotensin II.
ARTICLES
Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats
Pharmaceutical Research Department, F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
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