Angiotensin II‐mediated hippocampal hypoperfusion and vascular dysfunction contribute to vascular cognitive impairment in aged hypertensive rats

• Published in: Alzheimer's & dementia Vol. 20; no. 2; pp. 890 - 903
• Main Authors: Gannon, Olivia, Tremble, Sarah M., McGinn, Conor, Guth, Ruby, Scoppettone, Nadia, Hunt, Ryan D., Prakash, Kirtika, Johnson, Abbie C.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2024; John Wiley and Sons Inc
• Subjects: ACE inhibitors; Adults; Age; Aging; Alzheimer's disease; angiotensin II; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animal cognition; Animals; Antioxidants; Atrophy; Behavior; Blood flow; Blood Pressure; Brain; Captopril - pharmacology; Captopril - therapeutic use; Cerebrovascular disease; chronic hypertension; Cognitive ability; Cognitive Dysfunction - complications; Cognitive impairment; Dementia; Drinking water; Hemodynamics; Hippocampus; Hippocampus - metabolism; Hypertension; Hypertension - complications; Investigations; Ischemia; Laboratory animals; Male; Memory; Rats; Rats, Inbred SHR; Rats, Wistar; vascular cognitive impairment; vascular dementia; chronic hypertension; vascular cognitive impairment; aging; hippocampus; angiotensin II; vascular dementia
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.13491

INTRODUCTION Chronic hypertension increases the risk of vascular cognitive impairment (VCI) by ∼60%; however, how hypertension affects the vasculature of the hippocampus remains unclear but could contribute to VCI. METHODS Memory, hippocampal perfusion, and hippocampal arteriole (HA) function were investigated in male Wistar rats or spontaneously hypertensive rats (SHR) in early (4 to 5 months old), mid (8 to 9 months old), or late adulthood (14 to 15 months old). SHR in late adulthood were chronically treated with captopril (angiotensin converting enzyme inhibitor) or apocynin (antioxidant) to investigate the mechanisms by which hypertension contributes to VCI. RESULTS Impaired memory in SHR in late adulthood was associated with HA endothelial dysfunction, hyperconstriction, and ∼50% reduction in hippocampal blood flow. Captopril, but not apocynin, improved HA function, restored perfusion, and rescued memory function in aged SHR. DISCUSSION Hippocampal vascular dysfunction contributes to hypertension‐induced memory decline through angiotensin II signaling, highlighting the therapeutic potential of HAs in protecting neurocognitive health later in life. Highlights Vascular dysfunction in the hippocampus contributes to vascular cognitive impairment. Memory declines with age during chronic hypertension. Angiotensin II causes endothelial dysfunction in the hippocampus in hypertension. Angiotensin II‐mediated hippocampal arteriole dysfunction reduces blood flow. Vascular dysfunction in the hippocampus impairs perfusion and memory function.