Carotid bodies contribute to sympathoexcitation induced by acute salt overload

Abstract

Acute salt excess activates central osmoreceptors, which trigger an increase in sympathetic and respiratory activity. The carotid bodies also respond to hyperosmolality of the extracellular compartment, but their contribution to the sympathoexcitatory and ventilatory responses to NaCl overload remains unknown. To evaluate their contribution to acute NaCl overload, we recorded thoracic sympathetic (tSNA), phrenic (PNA) and carotid sinus nerve activities in decorticate in situ preparations of male Holtzman rats (60–100 g) while delivering intra-arterial infusions of hyperosmotic NaCl (0.17, 0.3, 0.7, 1.5 and 2.0 mol l−1; 200 μl infusion over 25–30 s, with a 10 min time interval between solutions) or mannitol (0.3, 0.5, 1.0, 2.7 and 3.8 mol l−1) progressively. The cumulative infusions of hyperosmotic NaCl increased the perfusate osmolality to 341 ± 5 mosmol (kg water)−1 and elicited an immediate increase in PNA and tSNA (n = 6, P < 0.05) in sham-denervated rats. Carotid body removal attenuated sympathoexcitation (n = 5, P < 0.05) but did not affect the tachypnoeic response. A precollicular transection disconnecting the hypothalamus abolished the sympathoexcitatory and tachypnoeic responses to NaCl overload (n = 6, P < 0.05). Equi-osmolar infusions of mannitol did not alter the PNA and tSNA in sham-denervated rats (n = 5). Sodium chloride infusions increased carotid sinus nerve activity (n = 10, P < 0.05), whereas mannitol produced negligible changes (n = 5). The results indicate that carotid bodies are activated by acute NaCl overload, but not by mannitol. We conclude that the carotid bodies contribute to the increased sympathetic activity during acute NaCl overload, whereas the ventilatory response is mainly mediated by hypothalamic mechanisms.

Medullary Noradrenergic Neurons Mediate Hemodynamic Responses to Osmotic and Volume Challenges

“…In addition, recent work has shown that the carotid bodies are activated by HSI. The carotid bodies contribute to the increase in sympathetic activity during acute HSI (da Silva et al, 2019).…”

Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons

“…Intravenous sodium chloride administration coordinately enhanced phrenic nerve bursting frequency and thoracic sympathetic neural burst amplitude in decorticate Holtzman rats, both effects of which were abolished by precollicular transection, supporting paraventricular and supraoptic nuclei mediate the effects . Carotid body removal prevented the enhancement of thoracic sympathetic nerve activity elicited by intravenous administration of sodium chloride, though failed to prevent tachypnea, supporting carotid body glomus cells may represent effective osmoreceptors (da Silva et al, 2019). Peripheral and central chemoreceptor driven augmentation of the respiratory, central pattern generator and sympathetic oscillators becomes synchronized and commonly coupled through coordinate and independent bulbobulbar, spinoreticular, and peripheral afferent inputs couple and synchronize central and peripheral chemoreceptor mediated augmentation of neuronal ensembles constituting the constituent generators, strengthened by direct interactions between overlapping propriobulbar interneuronal arrays constituting the respiratory rhythm and pattern generator, sympathetic oscillators, and cardiovagal premotoneurons (Molkov et al, 2017;Zoccal, 2015).…”

The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

“…This possibility is supported by a growing number of studies indicating that they are polymodal sensors, able to monitor the chemical composition of the arterial blood. More specifically, these studies have shown that besides promoting autonomic and respiratory adjustments in response to arterial hypoxemia (i.e., peripheral chemoreflex), the carotid bodies can respond to several other circulating stimuli such as leptin, angiotensin II, glucose, sodium chloride, insulin, adrenaline, and, also, inflammatory mediators (Allen, 1998;da Silva et al, 2019;Jendzjowsky et al, 2021Jendzjowsky et al, , 2018Katayama, 2016;Kumar and Prabhakar, 2012;Shin et al, 2019;Thompson et al, 2016). Regarding inflammatory mediators, studies reported that the carotid body of many species, including rats, cats and humans, expresses receptors for lysophosphatidic acid (LPA), IL-1β, IL-6, and TNF-α (Fernández et al, 2008;Jendzjowsky et al, 2018;Mkrtchian et al, 2012;Wang et al, 2002).…”

“…In this regard, the carotid body, classically known as the main peripheral monitor of the O 2 levels in the blood, has been considered a polymodal sensor due to its particular ability to detect diverse molecules present in the circulation, such as glucose, sodium chloride, hormones, and also, inflammatory mediators (Allen, 1998; da Silva et al, 2019; Jendzjowsky et al, 2018; Katayama, 2016; Kumar and Prabhakar, 2012; Thompson et al, 2016). In the context of inflammation, several pieces of evidence indicate that the carotid bodies might be involved in the intricate interplay between the immune system and the sympathetic nervous system.…”