Science1 publisher2 min readPublished
Silencing a breathing-control brain region returned hypertensive rats to normal blood pressure
University of Sao Paulo and Auckland teams found that a breathing-control brain region, the pFL, can tighten blood vessels in rats. They suggest the circuit could help explain why about 40 percent of medicated patients still have uncontrolled blood pressure.
The Scientist · Science desk
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What happened
- Turning the neurons on triggered other brain circuits that ultimately raised the animals' blood pressure.
- Using genetic engineering, the team switched the pFL neurons on and off while recording breathing nerve activity, sympathetic nerve activity and blood pressure.
- Normally the pFL does nothing for routine breathing; it drives the forceful exhalations of exercise, coughing and laughing.
- The region fires when carbon dioxide runs high or oxygen runs low, as it does during sleep apnea, which the authors say helps explain why apnea raises blood-pressure risk.
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Why it matters
- capability The carotid bodies are sensor cells in the neck, outside the brain, so a drug reaching them could switch the pFL off without a compound that crosses into brain tissue.
- exposure By tying blood pressure to a breathing-control circuit and the sympathetic nerves, the work points any future therapy at patients whose pressure is driven from the brain.
- constraint No drug yet hits the pFL on its own, and the open problem is reaching it without disturbing the other jobs these neurons do.
The vessel-tightening showed up only in the hypertensive rats. In those animals the pFL neurons were not just aiding breathing; they were also signalling blood vessels to constrict, something the researchers did not see in control rats without high blood pressure [8]. Then they ran the manipulation the other way.
"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," said Julian Paton, a physiologist at the University of Auckland [9].
The authors propose that pFL neurons connect shifts in breathing rhythm, which a person would not necessarily notice, to higher activity in the sympathetic nervous system, the fight-or-flight branch that helps set blood pressure [10]. They put the clinical problem plainly. "Given that around 50 percent of patients with hypertension have a neurogenic component, the challenge is to understand mechanisms generating sympatho-excitation in hypertension," the researchers wrote [11].
On treatment, Paton pointed to a target 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 said [12].
The experiment does not show any of this in people. It ran in rats, and the authors say it is likely but not certain that the same wiring operates in humans [15]. The share of medicated patients whose pressure stays high is a population estimate, not a number this study produced [5]. About a third of the world's people are thought to have high blood pressure [16]. It raises the risk of heart problems and has been linked to conditions such as dementia [17].
What to watch
- Results from the repurposed carotid-body drug the team says it is importing to quench those sensors.
- Whether human studies confirm the pFL circuit found in rats.
- Whether quenching the carotid bodies disturbs normal responses to low oxygen or high carbon dioxide.