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September 8, 2026ACS Pharmacology & Translational ScienceOpen Access

Purinergic P2X7 Receptor Antagonism Impairs Aerobic Capacity without Detectable Effect on Cardiac Adaptation to Exercise in Mice

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Why the study?

It was unknown whether systemic P2X7 receptor antagonism affects aerobic capacity and the structural adaptation of the heart to exercise.

Does P2X7 receptor antagonism with Brilliant Blue G impair aerobic capacity and cardiac adaptation to exercise in adult male Swiss mice?

Population

Adult male Swiss mice

Comparison

P2X7 antagonist Brilliant Blue G vs saline across sedentary or exercised conditions

Design

2 x 2 factorial design animal study

Follow-up

Approximately 4 weeks

Key result

P2X7 antagonism with Brilliant Blue G reduced V̇O2max and peak power independently of training, without detectably blunting the structural response of the heart to exercise.

Authors

NSNaiara de Souza SantosIFIzabel Feltrin FabroAAAna Paula Araújo

Discussion

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Overview

P2X7 blockade may impair aerobic performance in mice without affecting cardiac remodeling; leaves open translation to humans and therapeutic implications.

Structured PICO

Does P2X7 receptor antagonism with Brilliant Blue G impair aerobic capacity and cardiac adaptation to exercise in adult male Swiss mice?

P
Population
Adult male Swiss mice subjected to a 4-week physical conditioning program to assess the effects of P2X7 antagonism on aerobic capacity and cardiac adaptation.
I
Intervention
P2X7 antagonist Brilliant Blue G (BBG; 50 mg/kg) with or without physical conditioning (treadmill exercise on alternate days over approximately 4 weeks)
C
Comparator
Saline with or without physical conditioning
O
Outcome
Maximal oxygen uptake (V̇O2max), peak power, and myocardial cardiomyocyte volume density (Vv)surrogate

P2X7 antagonism impairs aerobic capacity without blunting the structural response of the heart to exercise in mice, suggesting a metabolic rather than structural limitation.

Limitations

  • The present sample size bounds rather than excludes an effect on cardiac adaptation
  • sample size bounds rather than excludes an effect on cardiac adaptation

Cite This Study

Santos et al. (2026) studied this question. Brilliant Blue G (BBG) vs. saline was evaluated on Maximal oxygen uptake (V̇O2max), power, and myocardial cardiomyocyte volume density (Vv). P2X7 antagonism with Brilliant Blue G reduced V̇O2max and peak power independently of training, without detectably blunting the structural response of the heart to exercise.

synapsesocial.com/papers/6aa2420201abe00586efa5cchttps://doi.org/10.1021/acsptsci.6c00422
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Purinergic Signaling in the Cardiovascular System2017 · 410 citations
  2. 2Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms2011 · 269 citations
  3. 3Stereological tools in biomedical research2003 · 595 citations