Sleep apnea, a condition characterized by pauses in breathing during sleep, is often associated with high blood pressure. This link raises concerns about the increased risk of heart problems for individuals with both conditions. Now, researchers have identified two brain chemicals that play a significant role in this connection, potentially paving the path for novel therapeutic approaches.
In a study published in *The Journal of Physiology*, scientists focused on oxytocin and corticotropin-releasing hormone (CRH), two brain-produced chemicals known for their influence on blood pressure. They investigated how these neurohormones affect the brainstem, a region at the base of the brain responsible for controlling various involuntary functions, including blood pressure.
Sleep apnea involves temporary cessation of breathing during sleep, depriving the body of oxygen. This creates a state of hypoxia, or low oxygen levels. Dr. David Kline, a professor at the University of Missouri College of Veterinary Medicine who led the study, explained that hypoxia triggers reflexes to increase breathing and elevate blood pressure to deliver oxygenated blood to vital areas.
While the effects of oxytocin and CRH on blood pressure are known, their role in response to these brief, recurrent hypoxic episodes was not fully understood. The researchers conducted an experiment with lab rats divided into two groups: one exposed to normal oxygen levels and the other intermittently subjected to low-oxygen conditions mimicking aspects of sleep apnea.
The experiment lasted for 10 days, after which the scientists analyzed the rats’ brainstems using various techniques to assess neuron activity. They also examined the activity of oxytocin and CRH using a microscope and manually counted specific brain cells that respond to these chemicals.
Both oxytocin and CRH are produced by cells in a structure called the paraventricular nucleus (PVN). These PVN cells connect to a major sensory center in the brainstem that receives signals from the body to regulate the cardiovascular system, including blood pressure. The experiment revealed that hypoxia enhances the influence of oxytocin and CRH in sending these signals.
The two chemicals had a more pronounced effect on the brainstem activity of the hypoxic rats compared to those kept at normal oxygen levels. After bouts of low oxygen, there was an increase in the release of these chemicals from the PVN and an increase in the number of receptors they bind to in the brainstem. Consequently, the brainstem’s sensory center exhibited an upsurge in the number of signals it sent out.
Based on these findings, Kline suggested that sleep apnea may amplify the effects of oxytocin and CRH on the brainstem, leading to elevated blood pressure. In other words, the release of these chemicals following hypoxic episodes causes blood pressure to rise progressively each time. Kline hypothesized that if this happens too frequently over weeks, blood pressure remains elevated due to alterations in the brain regions responsible for blood pressure control.
However, this study did not specifically investigate the mechanisms behind this phenomenon. The research group is currently conducting further studies to uncover these unknowns. Kline believes that once more chemicals involved in this mechanism are identified, specific drugs can be developed to target them and lower blood pressure in sleep apnea patients.
He emphasized that blanket drugs affecting the entire brain may not be the optimal approach, as the effects of oxytocin and CRH depend on the specific brain regions they interact with. Both chemicals can actually decrease blood pressure if they target different parts of the brainstem than the one studied in this research. However, in the region examined by the researchers, both chemicals had an elevating effect, according to Procopio Gama de Barcellos Filho, a postdoctoral researcher in Kline’s lab who led the study.
Kline expressed optimism that this basic research will lead to new avenues for clinicians and drug companies to explore. However, he cautioned that translating these findings into therapeutic approaches for human patients is still a long way off.
