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Aging exacerbates hypertension‐induced cerebromicrovascular injury in mice: role of autoregulatory dysfunction in the development of vascular cognitive impairment
Author(s) -
Toth Peter,
Tucsek Zsuzsanna,
Sosnowska Danuta,
Gautam Tripti,
Mitschelen Matthew,
Tarantini Stefano,
Deak Ferenc,
Koller Akos,
Sonntag William E,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1186.4
Subject(s) - hippocampal formation , neuroinflammation , medicine , angiotensin ii , microglia , endocrinology , blood pressure , hippocampus , inflammation
Hypertension in the elderly is a main risk factor for vascular cognitive impairment (VCI). To elucidate the mechanisms by which aging exacerbates the deleterious cerebrovascular effects of hypertension, young (3 mo) and aged (24 mo) C57/BL6 mice were infused with angiotensin II (AngII) for 4 weeks. In young hypertensive mice, pressure‐induced myogenic tone of middle cerebral arteries (MCA) was increased (due to an up‐regulation of the 20‐HETE/TRPC6 pathway). MCAs of aged AngII treated mice exhibited impaired functional adaptation to hypertension (decreased myogenic tone, autoregulatory dysfunction), which was associated with increased disruption of the blood‐brain barrier, hippocampal microvascular rarefaction, microglia activation, up‐regulated hippocampal expression of pro‐inflammatory cytokines and chemokines and impaired performance in tests relevant for hippocampally ‐dependent tasks of learning and memory. Taken together, aging exacerbates hypertension‐induced cerebromicrovascular injury in mice due to an age‐related autoregulatory dysfunction, which induces neuroinflammation and promotes the development of VCI.