RAS Inhibition Attenuates Cognitive Impairment by Reducing Blood- Brain Barrier Permeability in Hypertensive Subjects
Recent studies have suggested that blood-brain barrier (BBB) abnormalities are present from an early stage in
patients exhibiting mild symptoms of cognitive impairment during the development of hypertension. There is also
growing body of evidence suggesting the potential role of the renin-angiotensin system (RAS) in the pathogenesis of
small-vessel disease and cognitive impairment. However, the specific contribution of the RAS to BBB disruption and
cognitive impairment remains unclear. We found a significant leakage from brain microvessels in the hippocampus and
impaired cognitive functions in angiotensin II (AngII)-infused hypertensive mice, which were associated with increased
brain AngII levels. These changes were not observed in AngII-infused AT1a receptor (-/-) mice. We also observed that
Dahl salt-sensitive hypertensive rats exhibited hypertension, leakage from brain microvessels in the hippocampus, and
impaired cognitive function. In these animals, treatment with an AngII receptor blocker, olmesartan, did not alter blood
pressure, but markedly ameliorated leakage from brain microvessels and restored the cognitive decline. These data
support the hypothesis that RAS inhibition attenuates cognitive impairment by reducing BBB injury, which is independent
of blood pressure changes.
Keywords: Blood-brain barrier, cognitive impairment, hypertension, renin-angiotensin system (RAS), olmesartan.
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