Key result
Experimental hypertension induced by angiotensin II or aldosterone promoted blood-brain barrier dysfunction, leukocyte accumulation, and working memory impairment, which were prevented but not reversed by hydralazine.
Why the study?
Hypertension increases cognitive impairment risk and vascular inflammation, but whether immune cell infiltration occurs in the brain and links to cognitive decline was unknown.
Does hydralazine prevent or reverse brain inflammation and cognitive impairment in mice with angiotensin II-induced hypertension?
Does hydralazine prevent or reverse brain inflammation and cognitive impairment in mice with angiotensin II-induced hypertension?
In a mouse model, hypertension-induced brain inflammation and cognitive impairment can be prevented by early anti-hypertensive therapy but are not readily reversed once established.
Immune infiltration may link hypertension to cognitive impairment in mice; leaves open translation to human neuroinflammation-targeted therapies.
Background: 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. Methods: 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. 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. Conclusions: 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.
No takes yet. Share an insight, caveat, or question.
Dinh et al. (2025) studied Hypertension (n=218). Angiotensin II or aldosterone vs. Vehicle was evaluated on Brain inflammation, blood-brain barrier permeability, and working memory. Experimental hypertension induced by angiotensin II or aldosterone promoted blood-brain barrier dysfunction, leukocyte accumulation, and working memory impairment, which were prevented but not reversed by hydralazine.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: