Finding sheds light on importance of early life for health and may lead to clinical consequences for hypertension, such as new treatments
passing children periods of low oxygen in the first months of life – arising, for example, from episodes of sleep apnea – tend to develop breathing problems AND hypertension already in the juvenile stage and throughout adult life.
Researchers at the State University of São Paulo (Unesp) have demonstrated, for the first time, that in these cases the increase in blood pressure is due to a dysregulation of the autonomic nervous system – which works involuntarily to control blood pressure, heart rate, and breathing, among other factors.
The study, published in the journal Sleep Research Societywas performed in an animal model and demonstrated that increased blood pressure is associated with aa hyperactivity of neurons of the sympathetic nervous system (the branch of the autonomic nervous system that is activated in stressful situations).
“We found that rats that experienced episodes of intermittent hypoxia in the postnatal period had increased neuronal activity in the final part of the brainstem [bulbo] during young and adult life,” says Daniel Zoccal, professor at the Faculty of Dentistry of Araraquara (FOAr-Unesp).
“This is likely due to an adaptation of the brain resulting from the period of low oxygen during a critical stage of development. Among the adaptations is increased activity of the sympathetic autonomic nervous system, possibly due to increased expression of a protein called hypoxia-inducible factor (linked to the HIF-1a gene, is the absence of sufficient oxygen in the tissues to maintain bodily functions) in the neurons of the medulla”, says the specialist.
Possible new treatments for hypertension
According to the researcher, the increased expression of the HIF-1a protein by neurons in the medulla generates a series of changes in reading other genes which, between different actions, monitor cell activity. Consequently, neurons with higher expression of HIF-1a showed greater activity, resulting in smaller blood vessels and, therefore, higher blood pressure.
This phenomenon corresponds to what scientists call epigenetics, i.e. biochemical changes in cells caused by environmental stimuli that promote the activation or silencing of genes without causing changes in the individual’s genome.
In addition to demonstrating for the first time the mechanisms involved in the relationship between episodes of low oxygenation in postnatal life and hypertension in youth and adulthood, the work, supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), can lead important clinical implications.
“Although hypertension has a high prevalence – about 30% of the world’s population – its origin still needs to be better understood. It is only known that there is a risk associated with factors such as obesity, sedentary lifestyle, kidney problems and salt consumption , for example. With this discovery, we can study new treatments,” says Zoccal at Agência FAPESP.
Importance of the first years of life for health
The discovery also sheds light on the importance of an individual’s early life for disease development. “There is a need to watch children’s breathing more carefully also as a means of preventing the development of disease in later life,” he says.
Episodes of apnea in newborns can they occur more often in premature infantswhen the central nervous system and respiratory system are not yet fully mature, or in children with adenoid or tonsillar hyperplasia, some anatomical deformity, or obesity.
For the researcher, describing the whole process of how high blood pressure occurs due to low oxygenation in the postnatal period (up to about two years of age in humans) can also assist in finding treatment for those patients who do not respond well to antihypertensive drugs – about 20% of hypertensive patients.
Previous studies had already shown that hypertensive patients, especially those who do not respond to drug treatment, have increased electrical activity at the interface between sympathetic nerves and blood vessels. “The blood vessels of these individuals have a smaller caliber, which results in increased blood pressure,” he says.
Low oxygenation
In the study, the researchers hypoxia induced in rats during the first ten days of life. During this time, the animals experienced short-term hypoxic episodes, with oxygen depletion from 21% to 6% for 30 seconds. This happened every nine minutes during the animals’ sleep.
The generated simulation six episodes of sleep apnea per hour, which is equivalent to a case of moderate sleep apnea. “In the clinic there are cases of severe apnea where the patient experiences 30 or even 60 episodes per hour,” explains the researcher.
After two weeks, the simulations performed over eight hours a day ceased and the animals resumed breathing normally. When the animals completed 40 and 90 days of life – which in humans would be comparable to 13-16 and 40-50 years, respectively – the researchers evaluated physiological parameters such as blood pressure and heart rate.
At both ages, rats that experienced periods of intermittent hypoxia postnatally showed a consistent increase in blood pressure — between 10 and 20 millimeters of mercury (mmHg) above the control group.
According to the results, the mean blood pressure in juvenile rats was 84±7 mmHg in the control group, while in the intermittent hypoxia group it was 95±5 mmHg. The mean for the adult animals was 103±10 mmHg for the control group and 121±9 mmHg for the low oxygen episode group. It is worth noting that the indexes of blood pressure in both rodents and humans is similar.
“In the study we did not evaluate when the animals became hypertensive, we only verified that in the juvenile stage the rats already had alterations related to blood pressure and, in the adult stage, they were hypertensive,” explains the researcher.
Sympathetic and parasympathetic system
After concluding that intermittent hypoxia increased blood pressure in the animals, the researchers set out to investigate the contribution of the sympathetic nervous system in this process. It is worth mentioning that the autonomic nervous system is divided into two parts: the sympathetic and the parasympathetic.
In general, the sympathetic system is responsible for changes in the body in alert situations, preparing the body to face or flee from a threat. Therefore, it involves a greater expenditure of energy. It is up to this branch to increase heart rate and blood pressure, release adrenaline, dilate the bronchi, dilate the pupils, increase perspiration. The parasympathetic nervous system normalizes the functioning of internal organs after the alert situation.
By placing the electrodes in contact with the sympathetic nerves of young rats, the researchers observed that the animals that went through intermittent hypoxia had a greater amount of electrical impulses traveling through the sympathetic nerves than animals that did not go through episodes of low oxygenation. A pharmacological approach was used in adult rodents and achieved the same result as in the juvenile rat study.
“We used a drug that inhibits the actions of the sympathetic nervous system, and depending on the response of the drop in blood pressure, it was possible to infer that the sympathetic activity was increased,” says Zoccal.
The Unesp researchers also analyzed the activity of neurons in the medulla, a region of the brain that controls the vegetative functions of the body, such as heartbeat, respiration and the sympathetic activity of blood vessels.
“We focused our analysis on the ventral surface of the medulla, a region essential for generating sympathetic activity and maintaining normal blood pressure. [em humanos cerca de 12/8 mmHg]. And we observed that among animals that had undergone postnatal intermittent hypoxia, there is a higher firing rate of neurons in this region. This showed dysfunction in this group of marrow, caused by exposure to intermittent hypoxia, which maintains increased sympathetic activity, increasing blood pressure,” he explains.
The researchers also observed that, in addition to being more active, the Sympathetic nervous system neurons expressed more HIF-1a proteins. “This discovery allowed us to associate the whole process with a possible epigenetic cause,” he says.
The HIF-1a protein
Zoccal points out that the HIF-1a protein was studied by the winners of the 2019 Nobel Prize in Medicine. The winners found that when oxygen levels are low, the amount of this factor increases and induces cellular adaptations that ensure cell survival and of the body during hypoxic conditions. On the other hand, HIF-1a concentration decreases when oxygen levels are normal.
The study focused on the effects of postnatal intermittent hypoxia on blood pressure resulting from sympathetic nervous system dysfunction. However, it is known that changes in this system can lead to other changes. This is because sympathetic activity controls many bodily functions, including body temperature and, consequently, metabolism.
“In another study we published, using the same experimental model, we noticed that animals that underwent hypoxia were of lower weight than the control group, which could be a consequence of increased sympathetic activity.” , he claims.
‘We also observed that these animals began to exhibit respiratory irregularities, with an unusual pattern of acceleration and deceleration of breathing at rest. Therefore, in addition to being hypertensive, we saw that the animals may exhibit respiratory problems and possibly metabolic alterations,’ he concludes. . /AGÊNCIA FAPESP
Source: Terra
Ben Stock is a lifestyle journalist and author at Gossipify. He writes about topics such as health, wellness, travel, food and home decor. He provides practical advice and inspiration to improve well-being, keeps readers up to date with latest lifestyle news and trends, known for his engaging writing style, in-depth analysis and unique perspectives.
