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September 15, 2026Clinical ScienceOpen Access

Prehypertensive SHRs exhibit lower brain angiotensin 1-7 levels than Wistar rats, suggesting early hypertension predisposition.

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Why the study?

Aging is associated with hypertension, end-organ damage, and cognitive dysfunction, and it was unknown whether aging and hypertension are linked to region-specific changes in the brain ACE2/Ang-(1-7)/MasR axis.

Population

Wistar rats and spontaneously hypertensive rats at different ages

Comparison

Wistar rats vs spontaneously hypertensive rats across brainstem, hypothalamus, hippocampus, and cerebral cortex

Design

Animal experimental study

Key result

At a prehypertensive stage (1 month), SHRs exhibited lower Ang-(1-7) levels in multiple brain regions compared to Wistar rats, suggesting early abnormal changes may predispose to hypertension.

Authors

NMNatalia L Rukavina MikusicOCOrnella ConteEBEzequiel Bruna-Haupt

Discussion

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Overview

No immediate clinical implications from rat data; leaves open whether early brain ACE2 axis deficits drive human age-related hypertension.

Key Points

  • To determine whether aging and hypertension associate with region-specific changes in the brainstem, hypothalamus, hippocampus, and cerebral cortex ACE2/Ang-(1-7)/MasR axis in normotensive and spontaneously hypertensive rats.
  • Analyzed brainstem, hypothalamus, hippocampus, and cerebral cortex tissues from Wistar rats and spontaneously hypertensive rats (SHRs) at 1, 3, and 12 months of age.
  • Measured Ang-(1-7) levels via radioimmunoassay and quantified ACE2 and Mas receptor protein expression using immunoblotting.
  • In Wistar rats, Ang-(1-7) peptide levels decreased progressively with age across all four brain regions, whereas prehypertensive 1-month-old SHRs displayed significantly lower Ang-(1-7) levels than Wistar controls in all brain areas.
  • Prehypertensive SHRs demonstrated lower hypothalamic ACE2 and Mas receptor protein expression than age-matched Wistar controls, while brainstem Mas receptor expression was significantly higher in 1-month-old SHRs.
  • Ang-(1-7) levels showed no differences between rat strains at 3 and 12 months of age, driven by a transient increase in SHRs at 3 months that preceded a decrease by 12 months.

PICO

P
Population
Wistar rats and spontaneously hypertensive rats (SHRs) evaluated at 1, 3, and 12 months of age to assess region-specific changes in the brain ACE2/Ang-(1-7)/MasR axis.
E
Exposure / Comparator
Spontaneously hypertensive rats (SHRs) vs Wistar rats
O
Primary Outcome
Ang-(1-7) levels, ACE2 and MasR expression in brain regions

Cite This Study

Mikusic et al. (2026) studied Hypertension. Spontaneously hypertensive rats (SHRs) vs. Wistar rats was evaluated on Ang-(1-7) levels, ACE2 and MasR expression in brain regions. At a prehypertensive stage (1 month), SHRs exhibited lower Ang-(1-7) levels in multiple brain regions compared to Wistar rats, suggesting early abnormal changes may predispose to hypertension.

synapsesocial.com/papers/6aa90187eed42882c1fc19c6https://doi.org/10.1042/cs20261834
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Also Consider

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

  1. 1P181 AGE-RELATED CHANGES IN THE PROTECTIVE AXIS OF THE RENIN-ANGIOTENSIN SYSTEM IN THE BRAIN OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS2024
  2. 2Brain angiotensin in the developing spontaneously hypertensive rat1988 · 85 citations
  3. 3Regulation of angiotensin-converting enzyme 2 and Mas receptor by Ang-(1–7) in heart and kidney of spontaneously hypertensive rats2011 · 39 citations
  4. 4Differential Mechanisms of Ang (1‐7)‐Mediated Vasodepressor Effect in Adult and Aged Candesartan‐Treated Rats2011 · 43 citations
  5. 5Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats2006 · 68 citations