Direct angiotensin II type 2 receptor stimulation by compound 21 prevents vascular dementia

Journal of the American Society of Hypertension : JASH
Jun IwanamiMasatsugu Horiuchi

Abstract

Angiotensin II type 2 (AT(2)) receptor activation has been reported to play a role in cognitive function, although its detailed mechanisms and pathologic significance are not fully understood. We examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) could prevent cognitive decline associated with hypoperfusion in the brain.We employed a bilateral common carotid artery stenosis (BCAS) model in mice as a model of vascular dementia. The Morris water maze task was performed 6 weeks after BCAS operation. Azilsartan (0.1 mg/kg/day) or C21 (10 μg/kg/day) was administered from 1 week before BCAS. Cerebral blood flow (CBF) and inflammatory cytokine levels were also determined. Wild-type (WT) mice showed significant prolongation of escape latency after BCAS, and this cognitive impairment was attenuated by pretreatment with azilsartan. Cognitive impairment was more marked in AT(2) receptor knockout (AT(2)KO) mice, and the preventive effect of azilsartan on cognitive decline was weaker in AT(2)KO mice than in WT mice, suggesting that the improvement of cognitive decline by azilsartan may involve stimulation of the AT(2) receptor. The significant impairment of spatial learning after BCAS in WT mice was attenua...Continue Reading

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Citations

Jun 14, 2017·Medicinal Research Reviews·Mathias HallbergAnders Hallberg
Mar 15, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tauheed IshratSusan C Fagan
Aug 8, 2018·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masaki MogiMasatsugu Horiuchi
Feb 13, 2018·Journal of the American Heart Association·Akinori HigakiMasatsugu Horiuchi
May 19, 2017·Frontiers in Aging Neuroscience·Jose L Labandeira-GarciaMaria J Guerra
Nov 20, 2020·Clinical Science·U Muscha Steckelings, Colin Sumners
Oct 30, 2020·Frontiers in Neuroscience·Caglar CosardereliogluPeter M Abadir
Apr 10, 2021·Metabolic Brain Disease·Golnoush MirzahosseiniTauheed Ishrat
Jun 29, 2021·Frontiers in Cardiovascular Medicine·Lulu AnPoornima Venkat

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