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May 4, 2020HypertensionOpen Access

AT2R’s (Angiotensin II Type 2 Receptor’s) Role in Cognitive and Cerebrovascular Deficits in a Mouse Model of Alzheimer Disease

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Why the study?

It remained unknown whether AT4Rs act alone or with AT2Rs in mediating the cognitive and cerebrovascular benefits of angiotensin receptor blockers in Alzheimer disease models.

Does AT2R modulation improve cognitive and cerebrovascular deficits in a mouse model of Alzheimer disease?

Population

Transgenic mice overexpressing familial Alzheimer disease mutations of the human APP

Comparison

Losartan plus PD123319 vs losartan plus vehicle, and compound 21 vs vehicle

Design

Preclinical animal study

Authors

JRJessika RoyeaMLMaría Lacalle‐AuriolesLTLianne J. Trigiani

Discussion

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Overview

AT2R modulation fails to restore cognition or neurovascular function in AD mice; leaves open any therapeutic role in human disease.

Structured PICO

Does AT2R modulation improve cognitive and cerebrovascular deficits in a mouse model of Alzheimer disease?

P
Population
Transgenic mice overexpressing familial Alzheimer disease mutations of the human APP (amyloid precursor protein)
I
Intervention
Losartan (10 mg/kg per day, drinking water, 7 months) plus intracerebroventricular AT2R antagonist PD123319 (1.6 nmol/day, 1 month), or selective AT2R agonist compound 21 (intracerebroventricular: 1 nmol/day, 1 month or drinking water: 10 mg/kg per day, 7 months)
C
Comparator
Vehicle
O
Outcome
Spatial learning and memory, neurovascular coupling, oxidative stress, nitric oxide bioavailability, neuroinflammation, and Aβ pathologysurrogate

Targeting AT2Rs does not appear to be an effective strategy for restoring Aβ-related cognitive and cerebrovascular deficits in Alzheimer's disease models.

Cite This Study

Royea et al. (2020) studied this question.

synapsesocial.com/papers/6a8cec35bccdcede27ff1874https://doi.org/10.1161/hypertensionaha.119.14431
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cardiac Hypertrophy Is Associated With Decreased eNOS Expression in Angiotensin AT 2 Receptor–Deficient Mice2003 · 83 citations
  2. 2Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors2011 · 290 citations
  3. 3Angiotensin IV Receptors Mediate the Cognitive and Cerebrovascular Benefits of Losartan in a Mouse Model of Alzheimer's Disease2017 · 81 citations
  4. 4Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory2011 · 102 citations
  5. 5Neuropathological Alterations in Alzheimer Disease2011 · 3,452 citations