Abstract
Background and purpose: Hypertension increases the risk for cognitive
impairment and promotes vascular and renal inflammation. We tested if
immune cell infiltration occurs in the brain during hypertension and if
it is associated with cognitive impairment. Experimental approach: Male
C57Bl/6 mice were administered vehicle, angiotensin II (0.7 mg/kg/d
S.C.) or aldosterone (0.72 mg/kg/d S.C.) via osmotic minipumps. A subset
of mice also received hydralazine (50 mg/kg) in their drinking water
after minipump implantation. We measured systolic blood pressure,
markers of inflammation, working memory and transcriptomic changes in
the brain. Key results: Administration of angiotensin II or aldosterone
increased blood pressure and promoted blood-brain barrier dysfunction,
leukocyte accumulation and impairment of working memory in mice. When
co-administered with angiotensin II, hydralazine prevented the
development of these changes. In a separate cohort of mice in which
angiotensin II-induced changes were first established, intervention with
hydralazine lowered blood pressure but did not reverse brain
inflammation or cognitive impairment. Finally, angiotensin II infusion
altered the transcriptomic profile of the whole brain, as well as
specifically within the hippocampus, and co-treatment with hydralazine
modulated these changes. Conclusion and implications: Experimental
hypertension leads to brain inflammation and impaired working memory.
Cognitive impairment that develops during hypertension can be inhibited,
but not readily reversed, by anti-hypertensive therapy.