Cerebrovascular changes in chronic hypertension. Protective effects of enalapril in rats.
OBJECTIVE
Our recent study demonstrated that in chronic hypertension, hypertrophy of intracerebral arterioles was associated with an increase in the vascular extracellular matrix proteins: fibronectin, laminin, and collagen IV. An additional cerebral finding in chronic hypertension was hypertensive encephalopathy, in which breakdown of the blood-brain barrier (BBB) to serum proteins occurred in multifocal areas of the cortex and basal ganglia. This study was undertaken to determine which of these alterations were attenuated by antihypertensive therapy.


METHODS
Two weeks after the surgery to produce chronic renal hypertension, half the hypertensive rats were treated orally with enalapril (30 mg/kg), an angiotensin-converting enzyme inhibitor, for 5 weeks. Rats were perfusion-fixed, and their brains were removed and processed for morphological studies. The effect of treatment on vascular hypertrophy was assessed by quantitative morphometry and on the vascular extracellular matrix proteins and BBB permeability alterations by immunohistochemistry.


RESULTS
There was increased immunoreactivity for laminin, fibronectin, and collagen IV in pial and intracerebral arterioles of untreated hypertensive rats. Immunoreactivity was greatest in arterioles in areas with breakdown of the BBB to serum proteins. Enalapril treatment for 5 weeks resulted in a significant reduction of the mean systolic blood pressure, which was accompanied by attenuation of vascular hypertrophy and attenuation of changes in the vascular extracellular matrix proteins. In addition, there was reduction in the magnitude of BBB breakdown after treatment.


CONCLUSIONS
Enalapril treatment had a protective effect and attenuated vascular hypertrophy and the increase in vascular extracellular matrix proteins observed in chronic hypertension. In addition, there was reduction in the magnitude of BBB breakdown.
Nag
S
S
Department of Pathology, University of Toronto, Canada. nag@playfair.utoronto.ca
Kilty
D W
DW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002908:Chronic Disease; D004656:Enalapril / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D004656:Enalapril