Brain Region May Help Reverse High Blood Pressure

Research has uncovered evidence that a particular area of the brain may play a part in certain cases of high blood pressure.

Crucially, the findings also point to a possible means of reversing the effect.

A 2025 study by researchers from the University of São Paulo in Brazil and the University of Auckland in New Zealand found that the lateral parafacial (pFL) brain region can set off biological processes that increase blood pressure.

How the lateral parafacial region affects blood pressure

The pFL is associated with the control of breathing, particularly the strong, intentional exhalations made when exercising, coughing or laughing.

Experiments in rats showed that it may have another role too: constricting blood vessels.

The researchers suggest this pairing of respiratory control and blood-vessel signalling may contribute to hypertension in some instances.

It could help account for why so many people - around 40 percent, according to some estimates - continue to have uncontrolled blood pressure while taking anti-hypertensive medicines.

The study indicates that pFL neurons could connect alterations in breathing patterns, which may not be perceptible, with heightened sympathetic nervous system activity. This ‘fight-or-flight’ response helps regulate blood pressure, in line with earlier research associating hypertension with the brain and nervous system.

"Given that around 50 percent of patients with hypertension have a neurogenic component, the challenge is to understand mechanisms generating sympatho-excitation in hypertension," write the researchers in their published paper.

"Such a revelation would provide much-needed clinical orientation for new therapeutic strategies."

For their rat experiments, the team used genetic engineering methods to switch pFL neurons on and off before monitoring the consequences. They tracked breathing-related nerve activity, sympathetic nerve activity and blood pressure.

Activating pFL neurons in some rats stimulated further brain circuits, ultimately increasing the animals’ blood pressure.

The scientists could then chart brainstem and nerve activity in detail, including the other neurons communicating with the pFL region, and compare those measurements with results from control rats without hypertension.

In rats with hypertension, pFL neurons were not only supporting breathing but also causing blood vessels to narrow. The result identified a possible new route for treatment.

"We discovered that, in conditions of high blood pressure, the lateral parafacial region is activated and, when our team inactivated this region, blood pressure fell to normal levels," says physiologist Julian Paton, from the University of Auckland.

Breathing, sleep apnea and hypertension

These results also partly clarify why people with sleep apnea - breathing difficulties during the night - face an elevated risk of high blood pressure.

Again, the relationship is between respiration and blood flow. Although pFL neurons do not take part in ordinary breathing, they become active when carbon dioxide levels are high or oxygen levels are low, as happens in sleep apnea.

It is important to note that the work used animal models only. The same circuitry is likely to exist in humans, but this has not been confirmed.

Around one-third of the world’s population is thought to have high blood pressure, and many people cannot obtain medicines that could help. New treatment options are therefore urgently needed. Hypertension substantially raises the risk of numerous heart problems and has also been associated with several other conditions, including dementia.

Targeting carotid bodies rather than the brain

The next task is to establish how medicines could specifically target pFL neurons without disrupting other functions. The researchers say they have already made progress towards this goal.

Carotid bodies are groups of cells in the neck that function as small sensors and can affect pFL neurons from outside the brain. The team believes targeting these sensors could be sufficient to restrain the pFL region.

Paton explained the strategy: "Our goal is to target the carotid bodies, and we are importing a new drug that is being repurposed by us to quench carotid body activity and inactivate remotely the lateral parafacial region safely, i.e., without needing to use a drug that penetrates the brain."

The effort to affect carotid bodies from outside the brain may, however, be more advanced than that statement implies.

A separate study from the same University of Auckland group, published at the beginning of this year in Cardiovascular Research, reported that pyridoxal 5′ phosphate - the active form of vitamin B6 - blocks P2X3, a receptor that becomes overactive in the carotid bodies of people with high blood pressure. This reduces the nerve signals that cause blood pressure to rise in the first place.

In hypertensive rats, an infusion of the compound lowered blood pressure by an average of almost 16 mmHg.

A small trial involving 14 people with hypertension found that the same method reduced the body’s exaggerated reaction to low oxygen, at least among those whose chemoreflex was initially most sensitive.

This is not the same ‘new drug’ that Paton referred to as being repurposed, but it provides a second strand of evidence focused on precisely the same target. Unlike the rat research in this study, it has already been tested in people.

Although this approach may appear simpler than making a medicine penetrate the brain, it will still need extensive testing.

The research was published in Circulation Research.

This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. While we take pride in our process, we are only human. If you notice an error, please let us know.