Related Experiment Videos
Cerebrovascular changes in chronic hypertension. Protective effects of enalapril in rats
Insights
Enalapril treatment significantly reduced blood pressure in hypertensive rats, attenuating vascular hypertrophy and blood-brain barrier (BBB) breakdown. This study highlights enalapril
Area of Science:
- Neuroscience
- Cardiovascular Science
- Pharmacology
Background:
- Chronic hypertension causes intracerebral arteriole hypertrophy and extracellular matrix protein increases.
- Hypertensive encephalopathy involves blood-brain barrier (BBB) breakdown in chronic hypertension.
Purpose of the Study:
- To determine if antihypertensive therapy attenuates hypertension-induced cerebral alterations.
- To assess the protective effects of enalapril on vascular changes and BBB integrity.
Main Methods:
- Rats with chronic renal hypertension were treated with enalapril (an ACE inhibitor) for 5 weeks.
- Morphological studies, quantitative morphometry, and immunohistochemistry assessed vascular hypertrophy, extracellular matrix proteins, and BBB permeability.
Main Results:
- Untreated hypertensive rats showed increased laminin, fibronectin, and collagen IV in arterioles, particularly where BBB broke down.
- Enalapril treatment significantly reduced systolic blood pressure, vascular hypertrophy, and extracellular matrix protein changes.
- Enalapril also reduced the magnitude of blood-brain barrier breakdown.
Conclusions:
- Enalapril exhibits a protective effect against hypertension-induced vascular hypertrophy and extracellular matrix protein accumulation.
- Antihypertensive therapy with enalapril mitigates blood-brain barrier disruption in chronic hypertension.
Background And Purpose:
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.