Researchers discover that blood pressure sensors play a role in the immune response
Aortic baroreceptors, which are known for regulating blood pressure, have also been shown to detect inflammatory processes. This discovery may pave the way for new treatment strategies for cardiovascular and inflammatory diseases
A key finding of the study, published in June in Basic Research in Cardiology, is that baroreceptors – mechanical sensors responsible for detecting and controlling changes in blood pressure – also detect signs of inflammation in the body.
Lead researcher Fernanda Brognara explained that, although the interaction between the nervous and immune systems has been known for over a century, the mechanisms involved in this communication are still the subject of ongoing research.
Previous studies have demonstrated that immune system mediators, such as cytokines (signaling proteins), are detected by the nervous system, which translates immune status into neural activity. However, the hypothesis that aortic baroreceptors might be involved in this response was first investigated during Brognara’s doctoral studies at the Department of Physiology of USP’s Ribeirão Preto Medical School (FMRP).
According to the researcher, her doctoral dissertation provided initial evidence supporting the hypothesis that aortic baroreceptors may have a function beyond the classical description of regulating blood pressure.
During her postdoctoral work at USP’s Ribeirão Preto School of Nursing (EERP) under the supervision of professor Evelin Capellari Cárnio, Fernanda continued her research, focusing on “exploring more directly the presence of immune system mediators in the aortic depressor nerve”. This research led to the findings of the current study.
Techniques adapted for the delicate aortic nerve of rats
The study investigated the arterial baroreceptors present in the aortic arch (a curve in the aorta, the body’s main artery, located in the chest) and the aortic depressor nerve. The latter is responsible for transmitting information captured by these sensors to the brainstem, the part of the brain that connects to the spinal cord.
These baroreceptors are located in the aortic arch and the carotid sinus (a dilation of the carotid artery located below the jaw). They are sensitive to the stretching of arterial walls caused by an increase in blood pressure. When they detect this change, the baroreceptors trigger a reflex response to maintain blood pressure within a narrow range.
Fernanda explained that the aortic depressor nerve is “a sensory nerve that acts as the communication pathway connecting the aortic baroreceptors to the brainstem”. While the aortic baroreceptors are the anatomical sensors anchored in the wall of the aortic arch, the nerve is the sensory structure responsible for capturing the information generated by these local sensors and transmitting it to the central nervous system.
To analyze the molecular profile of the aortic depressor nerve, the team employed gene and protein expression techniques, along with immunofluorescence, a laboratory method that uses fluorescent dyes to identify molecules. The experiments compared animals that were treated with and without lipopolysaccharide, a toxic substance used in experimental models to induce systemic inflammation.
After adapting the methodologies to the extremely small structure of the aortic depressor nerve in rats, Fernanda said, “We were able to successfully optimize these techniques for this tissue.”
The neuroimmune sensory axis in continuous immune surveillance
The researcher continued the analysis of the results, showing that even under normal physiological conditions, the aortic depressor nerve exhibits key components of innate immune signaling. These components include receptors for pathogen recognition, adaptor proteins, activation proteins, cytokines, and their respective receptors. “This indicates that this nerve is in a state of continuous immune surveillance, ready to act quickly.”
When the animals were subjected to systemic inflammation, the researchers observed increased gene expression of inflammatory mediators directly in the aortic depressor nerve, reported Fernanda. The research team tracked the progression of this response over time in the aortic arch and nodose ganglion, a cluster of nerve cells located at the base of the skull. They identified a coordinated neuroimmune sensory axis.
Another surprising finding was the change in the nerve’s electrical activity during inflammation. Under normal conditions, electrical discharges occur during systole (the heart’s contraction phase) and are silent during diastole (the relaxation and dilation phase). However, during endotoxemia (systemic inflammation induced in the experimental model), activity increased precisely during cardiac relaxation and falling blood pressure.
“Physiologically, if the aortic depressor nerve were activated solely by mechanical stimuli, as classically described in the literature, its activity should decrease in response to a drop in blood pressure. However, since nerve activity increased, this suggests that the nerve was activated directly by inflammatory mediators circulating in the blood rather than by arterial stretching”, she explained.
Essential link for neuroimmune communication
For the research team, the main finding of this study overturns a long-standing dogma in cardiovascular physiology. “For over a century, baroreceptors have been known exclusively as sensors of mechanical stretch. However, we discovered that the afferents of the aortic baroreceptors (pathways that send electrical signals to the brainstem) also possess the cellular machinery necessary to act as immune sensors, responding directly to systemic inflammation”, said Fernanda, stating that her findings reposition these structures as an essential link in neuroimmune communication.
According to her, describing this neuroimmune circuit could contribute to future investigations into therapies that target cardiovascular and inflammatory diseases. She noted that strategies that have already been studied for treating hypertension, such as electrically activating baroreceptors, could also be analyzed from the perspective of immune system modulation.
“Activation of the aortic depressor nerve could stimulate anti-inflammatory reflex pathways, reducing pro-inflammatory cytokine levels in the blood and controlling inflammation in hypertension. As with hypertension, this new neuroimmune pathway could benefit several other cardiovascular and inflammatory diseases”, she suggested.
The article Aortic baroreceptor afferents as sensors for systemic inflammation is available at this link.
For more information: Fernanda Brognara, email: fernanda.brognara@usp.br
*Intern under the supervision of Simone Gomes
English version: Nexus Traduções, edited by Denis Pacheco
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