Novel Drug Attenuates the Progression of Heart Failure

According to the Heart Failure Society of America, heart failure affects more than 6 million people in the United States over the age of 20. It also accounts for more than 8% of all heart disease deaths in the country.

Studies have shown that certain parts of the body called peripheral chemoreceptors, which typically regulate breathing, can be hyperactive in people with heart failure, leading to worsening heart failure and problems such as sleep apnea.

One of these peripheral chemoreceptors is the carotid body, a cluster of sensors near the carotid artery in the throat. In response to reduced blood flow and oxygen circulation, the sensors trigger rapid breathing and increased blood pressure by activating the sympathetic (“fight-or-flight”) nervous system.

In a new study published in Nature Communications, researchers looked at a way to reduce the damaging sympathetic activity of the carotid bodies by using a drug instead of removing them.

The researchers induced heart failure in juvenile (4 weeks old) male Wistar rats. They then examined petrosal neurons in heart failure rats and other rats. A petrosal neuron is a type of nerve cell that acts as a “wire” between the carotid body and the central nervous system.

The researchers reported that these neurons had more P2X3 receptors in the rats with heart failure than in the rats without heart failure.

They also observed spontaneous bursts of nerve activity in the carotid sinus nerve that were associated with breathing problems and increased heart rate.

Based on their observations, the researchers deduced that these bursts of nerve activity occurred when the carotid body released the chemical transmitter adenosine triphosphate, which then acted on the P2X3 receptors.

The researchers gave the rats a drug called AF-130, which blocks the P2X3 receptors and stops the bursts of nerve activity.

AF-130 treatment restored normal breathing patterns in rats with heart failure and lowered the number of apnea episodes.

AF-130 also improved heart function in rats with heart failure. 

AF-130 also reduced levels of the inflammatory cytokine interleukin (IL)-1β, suggesting that the drug has the potential to reduce inflammation.

Tassos Lymperopoulos, PhD, an associate professor of pharmacology at Nova Southeastern University in Florida said that it remains to be seen whether the results in rats will translate to heart failure in humans, but he wondered whether AF-130 could potentially be superior to beta-blockers.

“Since systemic inflammation goes down with AF-130 and the drug’s cytokine profile seems favorable, it would be interesting to see if the drug also has anti-atherosclerotic effects”. “If that’s the case, its therapeutic value in post-heart attack heart failure treatment will increase exponentially”.


Lataro, R.M., Moraes, D.J.A., Gava, F.N. et al. P2X3 receptor antagonism attenuates the progression of heart failure. Nat Commun 14, 1725 (2023). 
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