A fresh piece of research has uncovered evidence suggesting a specific brain region might contribute to certain instances of elevated blood pressure. Importantly, a method to potentially reverse this effect may also exist. The study’s findings are detailed in the journal Circulation Research.
According to the investigation conducted by a team from the University of São Paulo in Brazil and the University of Auckland in New Zealand, the lateral paragigantocellular nucleus of the medulla (pFL) could be inducing biological changes that lead to increased blood pressure.
The pFL region is implicated in the regulation of breathing—specifically, the forceful, directed exhalations that occur during exercise, coughing, or laughter.
In tests carried out on rats, the researchers observed that this structure also possessed the capability to constrict blood vessels.
Researchers posit that in certain cases, this interaction between breathing control and the signals communicated to the blood vessels could be the underlying cause of hypertension. This might account for why, in many individuals (estimated by some to be around 40 percent), blood pressure remains uncontrolled despite the use of antihypertensive drugs.
The study indicates that pFL neurons might be linking alterations in breathing rhythm—which may not even be consciously perceived—to heightened activity in the sympathetic nervous system (our “fight or flight” response), which is instrumental in managing blood pressure. This aligns with prior research connecting hypertension to the brain and nervous system.
“Given that roughly 50 percent of hypertensive patients have a neurogenic component, the objective is to decipher the mechanisms generating sympathetic activation in hypertension,” the researchers state. “Such a discovery would provide a much-needed clinical foundation for novel therapeutic strategies.”
In their rat experiments, the scientists employed genetic engineering techniques to either activate or deactivate pFL neurons, subsequently monitoring the outcomes. They tracked breathing-related neural activity, sympathetic nerve activity, and blood pressure readings.
When researchers stimulated the pFL neurons in a subset of rats, it triggered other brain circuits that ultimately elevated the animals’ blood pressure.
Following this, they were able to meticulously map the activity in the brainstem and nervous system, identifying other neurons with which the pFL area interacted, and contrasting this data with readings taken from control rats without hypertension.
In the hypertensive rats, the pFL neurons were found not only to aid in respiration but also to cause vasoconstriction. This finding also opened up a new potential avenue for treatment.
“We observed that the lateral paragigantocellular nucleus becomes active when blood pressure is high, and when our team turned this area off, the blood pressure returned to normal levels,” noted physiologist Julian Paton from the University of Auckland.
The results presented here also partially shed light on why individuals suffering from sleep apnea—episodes of breathing disruption during sleep—also face an increased risk of developing high blood pressure.
The common thread here is once again the linkage between respiration and blood flow: even though pFL neurons are not involved in typical breathing, they become engaged in response to elevated CO2 levels or reduced oxygen, conditions that characterize sleep apnea.
It is crucial to remember that this study utilized only animal models; while it is probable, it is not certain that the identical neural network is engaged in humans.
However, considering that approximately one-third of the global population struggles with high blood pressure, and many lack access to effective medications, the need for alternative treatments is pressing. Hypertension significantly escalates the risk of numerous cardiovascular ailments and is associated with many other conditions, such as dementia.
The next step involves determining how medications could specifically target pFL neurons without affecting other structures—and the researchers report making headway in this area as well.
The carotid bodies are clusters of cells situated in the neck area that function as minute sensors and appear capable of influencing pFL neurons from outside the brain. The researchers theorize that modulating these sensors might be enough to gain control over the pFL region.
“Our objective is to target the carotid bodies, and we are bringing in a novel compound that we are repurposing to suppress the activity of the carotid bodies and remotely and safely inactivate the lateral paragigantocellular nucleus—meaning without needing a drug that penetrates the brain,” explained Paton.
While this strategy might seem more straightforward than achieving drug penetration into the brain, it will still necessitate extensive trials.
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