Hypertension Allows Harmful Immune Cell Infiltration of the Brain
The high blood pressure of hypertension is harmful to tissues throughout the body. Pressure damage directly damages tissue structure, disrupts tissue function, and alters cell behaviors for the worse. This is particularly harmful to the brain, as brain tissue has only a limited capacity for regeneration following rupture of small blood vessels and consequent cell death. More subtly, increased pressure disrupts the normal operation of the blood-brain barrier that lines blood vessels passing through the brain. This allows leakage of inappropriate cells and molecules into the brain to provoke persistent inflammation, an important contribution to neurodegenerative conditions.
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. Male C57Bl/6 mice were administered angiotensin II or aldosterone as an experimental model of hypertension. This increased blood pressure and promoted blood-brain barrier dysfunction, leukocyte accumulation in the brain, and impairment of working memory.
When co-administered with angiotensin II, the antihypertensive medication 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.
In conclusion, experimental hypertension leads to brain inflammation and was associated with impaired working memory. Cognitive impairment that develops during hypertension can be inhibited, but not readily reversed, by anti-hypertensive therapy.