Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation

Abstract

Recent studies demonstrated a critical functional connection between the autonomic (sympathetic and parasympathetic) nervous and the immune systems. The carotid sinus nerve (CSN) conveys electrical signals from the chemoreceptors of the carotid bifurcation to the central nervous system where the stimuli are processed to activate sympathetic and parasympathetic efferent signals. Here, we reported that chemoreflex activation via electrical CSN stimulation, in conscious rats, controls the innate immune response to lipopolysaccharide attenuating the plasma levels of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin 1β (IL-1β) and interleukin 6 (IL-6). By contrast, the chemoreflex stimulation increases the plasma levels of anti-inflammatory cytokine interleukin 10 (IL-10). This chemoreflex anti-inflammatory network was abrogated by carotid chemoreceptor denervation and by pharmacological blockade of either sympathetic - propranolol - or parasympathetic - methylatropine – signals. The chemoreflex stimulation as well as the surgical and pharmacological procedures were confirmed by real-time recording of hemodynamic parameters [pulsatile arterial pressure (PAP) and heart rate (HR)]. These results reveal, in conscious animals, a novel mechanism of neuromodulation mediated by the carotid chemoreceptors and involving both the sympathetic and parasympathetic systems.

Increased lipopolysaccharide‐induced hypothermia in neurogenic hypertension is caused by reduced hypothalamic PGE2 production and increased heat loss

“…The reduction in baseline MAP in SHR submitted to CB removal is in line with the existing evidence indicating that aberrant peripheral chemoreflex activity causes sympathetic overactivity and hypertension in SHR (McBryde et al 2013;Pijacka et al 2018). A series of recent studies using the experimental model of LPS-induced SI reported the mandatory role of CBs not only in cardiovascular changes, but also in SI (Fernandez et al 2014;Santos-Almeida et al 2017;Amorim et al 2019). Worthy of note, the pharmacological modulation of CB activity during SI in hypertensive patients is a possible clinical target for these patients.…”

“…Therefore, the present study aimed to investigate the relationship between SI and hypertension with respect to thermoregulatory and cardiovascular control, as well as its putative mechanisms. We also examined the contribution of the carotid bodies (CBs); the polymodal receptors involved in the SI signalling and in the pathogeny of hypertension (Fernandez et al 2014;Santos-Almeida et al 2017;Paton et al 2013;Pijacka et al 2016) in thermoregulatory and cardiovascular changes during SI in SHR. We hypothesized that the brain-mediated thermoeffector mechanisms expected to be recruited during SI in normotensive rats are altered in SHR, causing atypical thermoregulatory responses in these animals.…”

Carotid sinus nerve stimulation attenuates alveolar bone loss and inflammation in experimental periodontitis

“…Our laboratory developed a technique to electrically stimulate the CSN in unanesthetized rats, providing simultaneous carotid baroreflex and chemoreflex activation without the undesirable effects of anesthesia 30 . In addition, both chemoreflex and baroreflex activation, through the CSN electrical stimulation, can also be used as an electroceutical approach to control the inflammation 24 . Despite that, little is known about the possible influence of the baroreflex and chemoreflex mechanisms, particularly their activation, on the hemodynamic parameters (MAP and HR) in PD.…”

Nerve Stimulation: Immunomodulation and Control of Inflammation

“…Specifically, high-frequency electroacupuncture on ST36 inhibits carrageenan-induced paw inflammation through pre-ganglionic innervations of the adrenal glands in rodents [61, 62]. By contrast, low-frequency electroacupuncture on ST36 in rodents inhibits inflammation in experimental models of paw swelling, lung leukocyte migration, surgical trauma, sepsis or arthritis, through local sympathetic post-ganglionic innervations, independent of the adrenal glands [63–66]. Thus, high-frequency electroacupuncture appears to activate pre-ganglionic innervations of the adrenal medulla to induce systemic catecholamines, whereas low-frequency electroacupuncture appears to activate specific sympathetic post-ganglionic innervations to induce local release of neurogenic norepinephrine[61].…”