A specific brain region known as the lateral parafacial (pFL) region can trigger biological changes that raise blood pressure, according to a 2025 study carried out by a team from the University of São Paulo in Brazil and the University of Auckland in New Zealand. Researchers found that this neural circuitry tightens blood vessels and links breathing control to the sympathetic nervous system, potentially driving hypertension in cases where standard medications fail.
University of São Paulo and University of Auckland Experiments Map Brainstem and Nerve Activity
In tests carried out on rats, researchers used genetic engineering techniques to turn pFL neurons on or off while monitoring breathing-related nerve activity, sympathetic nerve activity, and blood pressure. When the team activated pFL neurons, it triggered other brain circuits that ultimately raised the animals’ blood pressure. In hypertensive rats, these neurons did not just assist with breathing, but also actively constricted blood vessels.
The lateral parafacial region is linked to breathing control, specifically the forceful and deliberate exhalations that happen during exercise or when someone coughs or laughs. While pFL neurons are not involved in normal breathing, they fire up in response to high carbon dioxide or low oxygen levels.
Julian Paton Explains How Inactivating the Lateral Parafacial Region Drops Blood Pressure
The findings help explain why individuals who experience sleep apnea—problems breathing during the night—face a higher risk of high blood pressure. Around 50 percent of patients with hypertension have a neurogenic component, according to the published paper in Circulation Research, making the identification of sympatho-excitation mechanisms a critical clinical challenge.
“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.
Pyridoxal 5′ Phosphate Targets Carotid Bodies to Lower Blood Pressure
With roughly a third of the global population experiencing high blood pressure, the search for new treatment options remains urgent. The next challenge involves figuring out how drugs can target pFL neurons directly without interfering with other functions. Researchers believe that targeting tiny clusters of cells in the neck called carotid bodies might keep the pFL region in check from outside the brain.
“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,” Paton explained.
A separate study published earlier in Cardiovascular Research by the same University of Auckland group found that pyridoxal 5′ phosphate, the active form of vitamin B6, blocks the P2X3 receptor that becomes overactive in the carotid bodies of people with high blood pressure. In hypertensive rats, infusing this compound dropped blood pressure by an average of almost 16 mmHg. A small trial involving 14 people with hypertension demonstrated that the same approach eased the body’s exaggerated response to low oxygen among those with the most sensitive chemoreflexes.
Frequently Asked Questions About Brain-Driven Hypertension
What is the lateral parafacial (pFL) region?
The pFL is a brain region linked to breathing control, particularly forceful exhalations during exercise, coughing, or laughing. Research shows it also influences blood vessel constriction and sympathetic nervous system activity.
Why do people with sleep apnea have a higher risk of high blood pressure?
pFL neurons fire up in response to high carbon dioxide or low oxygen levels, which occurs during sleep apnea events. This connects breathing disruptions directly to blood flow and blood pressure spikes.
How does pyridoxal 5′ phosphate affect blood pressure?
Pyridoxal 5′ phosphate blocks the P2X3 receptor in the carotid bodies located in the neck. In testing, it dialed down nerve signals driving up blood pressure, dropping readings by an average of almost 16 mmHg in hypertensive rats.
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