Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.
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.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
Kuhn
H
H
Hefti
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D017315:Cilazapril; D008297:Male; D009929:Organ Size; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation
D011724:Pyridazines; D017315:Cilazapril