Abstract

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2 and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.

Highlights

  • The detection of oxygen (O2), carbon dioxide (CO2) and proton (H+) levels in arterial blood is crucial for the control of breathing (Prabhakar, 2000; Teppema and Dahan, 2010; Guyenet and Bayliss, 2015; Guyenet et al, 2019)

  • Our results show that the ventilatory responses to HX alone and HC alone were additive in SHAM rats and that this additivity was lost in carotid sinus nerve transection (CSNX) rats, suggesting that peripheral carotid body (CB) chemoafferent activity plays an essential role in determining the interactions between peripheral and central chemoafferent pathways controlling ventilation

  • Our data suggests that juvenile rats with prior CSNX possess a functional secondary means of low O2 sensing, other than the CB-carotid sinus nerve (CSN) complex, that send signals to respiratory control centers of the brainstem to trigger downstream respiratory reflexes

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Summary

Introduction

The detection of oxygen (O2), carbon dioxide (CO2) and proton (H+) levels in arterial blood is crucial for the control of breathing (Prabhakar, 2000; Teppema and Dahan, 2010; Guyenet and Bayliss, 2015; Guyenet et al, 2019). Arterial hypoxia (low pO2), hypercapnia (high pCO2) and/or acidosis (high H+ levels) stimulate breathing, which is essential for maintaining proper oxygenation of tissues. This ventilatory adjustment depends critically on the O2-sensing ability of the carotid bodies (CBs) and respiratory control brainstem nuclei (Prabhakar, 2000). CSN chemoafferents relay these signals to the commissural nucleus tractus solitarius (cNTS) within the brainstem (Song et al, 2011), and increased inputs from these chemoafferent fibers trigger downstream responses to restore arterial blood gas status and hemodynamic homeostasis (Prabhakar, 2000; Nurse, 2005, 2010)

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