P2X3 receptor antagonism attenuates the progression of heart failure

Area of Science:

• Cardiovascular Science
• Neuroscience
• Respiratory Medicine

Background:

• Heart failure (HF) has a poor prognosis despite treatment advances, with no cure.
• HF involves cardiac dysfunction, autonomic imbalance, inflammation, and sleep-disordered breathing.
• Peripheral chemoreceptor dysfunction exacerbates HF morbidities.

Purpose of the Study:

• To investigate the role of carotid body activity in heart failure pathogenesis.
• To explore the therapeutic potential of targeting purinergic receptors in the carotid body for HF treatment.

Main Methods:

• Utilized male rat models of heart failure.
• Measured carotid body discharges and peripheral chemoreceptor sensitivity.
• Investigated the role of P2X3 receptors using antagonism.

Main Results:

• Heart failure induced spontaneous, episodic carotid body discharges linked to disordered breathing.
• P2X3 receptors were upregulated in carotid body afferents in HF.
• Antagonizing P2X3 receptors normalized breathing, autonomic balance, cardiac function, and reduced inflammation.

Conclusions:

• Aberrant ATP signaling in the carotid body, mediated by P2X3 receptors, drives HF progression.
• Targeting carotid body P2X3 receptors offers a novel therapeutic strategy for reversing multiple HF pathologies.