Loss of ganglioglomerular nerve input to the carotid body impacts the hypoxic ventilatory response in freely-moving rats

Abstract

The carotid bodies are the primary sensors of blood pH, pO2 and pCO2. The ganglioglomerular nerve (GGN) provides post-ganglionic sympathetic nerve input to the carotid bodies, however the physiological relevance of this innervation is still unclear. The main objective of this study was to determine how the absence of the GGN influences the hypoxic ventilatory response in juvenile rats. As such, we determined the ventilatory responses that occur during and following five successive episodes of hypoxic gas challenge (HXC, 10% O2, 90% N2), each separated by 15 min of room-air, in juvenile (P25) sham-operated (SHAM) male Sprague Dawley rats and in those with bilateral transection of the ganglioglomerular nerves (GGNX). The key findings were that 1) resting ventilatory parameters were similar in SHAM and GGNX rats, 2) the initial changes in frequency of breathing, tidal volume, minute ventilation, inspiratory time, peak inspiratory and expiratory flows, and inspiratory and expiratory drives were markedly different in GGNX rats, 3) the initial changes in expiratory time, relaxation time, end inspiratory or expiratory pauses, apneic pause and non-eupneic breathing index (NEBI) were similar in SHAM and GGNX rats, 4) the plateau phases obtained during each HXC were similar in SHAM and GGNX rats, and 5) the ventilatory responses that occurred upon return to room-air were similar in SHAM and GGNX rats. Overall, these changes in ventilation during and following HXC in GGNX rats raises the possibility the loss of GGN input to the carotid bodies effects how primary glomus cells respond to hypoxia and the return to room-air.

Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing

“…All data are presented as the mean ± SEM and were analyzed using one-way and two-way ANOVA and Bonferroni corrections for multiple comparisons between means using the error mean square terms generated using the ANOVA analyses ( Getsy et al, 2023a ; Getsy et al, 2023b ). A p < 0.05 value was the initial level of significance that was modified according to the number of between-mean comparisons ( Getsy et al, 2023a ; Getsy et al, 2023b ).…”

“…All data are presented as the mean ± SEM and were analyzed using one-way and two-way ANOVA and Bonferroni corrections for multiple comparisons between means using the error mean square terms generated using the ANOVA analyses ( Getsy et al, 2023a ; Getsy et al, 2023b ). A p < 0.05 value was the initial level of significance that was modified according to the number of between-mean comparisons ( Getsy et al, 2023a ; Getsy et al, 2023b ). The modified t- statistic for two groups, for instance, is t = (mean group 1 ˗ mean group 2)/[s × (1/n 1 + 1/n 2 ) 1/2 ], where s 2 represents the mean square within groups term from the ANOVA and n 1 and n 2 are the number of rats in each group being compared.…”

Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge

“…Ventilatory parameters in freely-moving male mice were recorded by whole body plethysmography (PLY3223; Data Sciences International , St. Paul, MN) as described previously ( Palmer et al, 2013a ; b , 2015 ; Gaston et al, 2014 ; Getsy et al, 2014 ; Getsy et al, 2002 ; Getsy et al, 2023a ; Getsy et al, 2023b ). The parameters recorded and derived ( Supplementary Table S1 ; Supplementary Figure S2 ) were frequency of breathing (Freq); tidal volume (TV, volume of inspired air per breath); minute ventilation (Freq x TV, total volume of air inspired/min); inspiratory time (Ti, duration of inspiration); expiratory time (Te, duration of expiration); expiratory/inspiratory time (Te/Ti, expiratory quotient); end inspiratory pause (EIP, pause between end of inspiration and start of expiration); end expiratory pause (EEP, pause between end of expiration and start of inspiration); peak inspiratory flow (PIF); peak expiratory flow (PEF); airflow at 50% expired TV (EF 50 ); relaxation time (RT, time to exhale 64% of TV); expiratory delay (Te-RT); inspiratory drive (TV/Ti); expiratory drive (TV/Te); non-eupneic breathing index (NEBI, % of breaths non-eupneic breaths including irregular breaths, apneas and type 1 and 2 sighs); and NEBI/Freq (NEBI corrected for Freq).…”

“…We then determined the mean and SEM of the group data. All between-group data were analyzed by one-way ANOVA ( Getsy et al, 2023a ; Getsy et al, 2023b ). Statistical analyses were performed using GraphPad Prism software (Version 9.5.1–2023; GraphPad Software , Inc., La Jolla, CA, United States).…”

“…To our knowledge, there are no studies that have directly addressed whether HDAC6 has a role in signaling processes involved in the ventilatory responses that occur upon exposure to HX gas challenge. As such, the objective of this study was to compare the ventilatory responses elicited by a HX gas challenge (10% O 2 , 90% N 2 ) in adult male wildtype (WT) C57BL/6 mice and HDAC6 knock-out (KO) mice by whole body plethysmography ( Palmer et al, 2013a ; Palmer et al, 2013b ; Palmer et al, 2015 ; Gaston et al, 2014 ; Getsy et al, 2014 ; Getsy et al, 2023a ; Getsy et al, 2023b ). The data from these studies demonstrate that HDAC6 has an important role in regulating the neural responses that drive the ventilatory responses to HX gas challenge.…”