Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino‐aortic denervated rats

Abstract

What is the central question of this study? Sino-aortic denervated (SAD) rats present normal levels of sympathetic activity and mean arterial pressure. However, neural mechanisms regulating the sympathetic activity in the absence of arterial baroreceptors remain unclear. Considering that respiration modulates the sympathetic activity, we hypothesize that changes in the respiratory network contribute to keep the sympathetic outflow in the normal range after removal of arterial baroreceptors. What is the main finding and its importance? Despite longer inspiration observed in SAD rats, the respiratory-sympathetic coupling is working within a normal range of variation. These findings suggest that in the absence of arterial baroreceptors the respiratory modulation of sympathetic activity is maintained within the normal range. The activity of presympathetic neurons is under respiratory modulation, and changes in the central respiratory network may impact on the baseline sympathetic activity and mean arterial pressure. It is well known that after removal of baroreceptor afferents [sino-aortic denervation (SAD)], rats present an unexpected normal level of mean arterial pressure. We hypothesized that changes in the respiratory pattern and in the respiratory modulation of the sympathetic activity contribute to keep the sympathetic outflow within a normal range of variation in the absence of arterial baroreceptors in rats. To study these mechanisms, we recorded perfusion pressure and the activities of phrenic and thoracic sympathetic nerves in male juvenile rats using the working heart-brainstem preparation. The time of inspiration significantly increased in SAD rats, and this change was not dependent on the carotid bodies or on the vagal afferents. However, no changes were observed in the perfusion pressure or in the baseline thoracic sympathetic nerves in all phases of the respiratory cycle in SAD rats. Our data show that despite longer inspiratory activity, the baseline sympathetic activity is maintained at a normal level in SAD rats. These findings indicate that the respiratory-sympathetic coupling is normal after SAD and suggest that the respiratory modulation of sympathetic activity is maintained within the normal range after the removal of arterial baroreceptors.

Firing properties of ventral medullary respiratory neurons in sino‐aortic denervated rats

“…It is postulated that the increase of the Abd nerve activity during hypercapnia is dependent on the activity of neurons located in the retrotrapezoid nucleus/parafacial respiratory group, because the pharmacological inactivation of these regions abolishes the active expiration during a hypercapnic stimulus (Abdala et al., ). The results of the present study show the emergence of active expiration accompanied by a reduction in the time of inspiration in SAD and Sham rats during hypercapnia, whereas the respiratory‐related sympathetic response was different between SAD and Sham during the same experimental protocol (Amorim et al., ). These findings suggest that CO 2 might differentially potentiate the respiratory (abdominal and phrenic) and sympathetic activities in Sham and SAD rats.…”

“…Previous studies from our laboratory documented that at least three subpopulations of presympathetic neurons displayed respiratory‐related activity, including neurons that are inhibited during inspiration (Moraes et al., ). Considering the longer inspiration in SAD rats (Amorim et al., ), we suggest that this subpopulation of inspiratory‐inhibited rostral ventrolateral medulla presympathetic neurons (Moraes et al., ) should receive a respiratory‐related inhibition for a longer time in SAD than in Sham rats, buffering an increase in sympathetic activity and arterial pressure in SAD rats.…”

“…The higher HR in SAD rats is probably attributable to changes in the autonomic balance to the heart. Regarding the baseline sympathetic activity, we previously showed that there is no increase in the baseline sympathetic activity during inspiration, E‐1 and E‐2 phases of the respiratory cycle in SAD rats (Amorim et al., ).…”

“…In a previous study, we documented that during hypercapnia rats exhibited a significant reduction in the time of inspiration, which was more evident in SAD than in Sham rats. Moreover, a hypercapnic challenge increased the sympathetic activity in all phases of the respiratory cycle in Sham, whereas this increase was more pronounced during inspiration in SAD rats (Amorim et al., ). This change in the sympathetic response of SAD rats during hypercapnia might be indicative of desensitization of central chemoreceptors to CO 2 , probably attributable to an increase in the baseline arterial partial pressure of CO 2 observed in conscious SAD rats (Amorim et al., ).…”

“…In previous studies, using conscious rats and an in situ preparation, we documented that rats submitted to baroreceptor afferent removal [sino‐aortic denervation (SAD)] exhibit a significant reduction in the respiratory frequency and minute ventilation (Amorim, Bonagamba, Souza, Moraes, & Machado, ), accompanied by longer inspiration (Amorim, Bonagamba, Souza, Moraes, & Machado, , ). These previous studies indicate that after baroreceptor afferent removal, rats exhibit a reconfiguration of the respiratory network, ultimately leading to changes in breathing at rest (Amorim et al., , ). These observations raise the hypothesis that after SAD, ventral medullary respiratory neurons change their firing properties, which might drive longer inspiration.…”