The interaction between chemoreflex and baroreflex plays a pivotal role in physical exertion during hypobaric hypoxia in rats

The current doctoral theses i son base of two publications, which has an objective Determine the contribution of CB glomus cells to peak O2 uptake (V O2peak) during exercise in rats using a chemogenetic inhibition approach and to investigate the impact of prolonged exogenous OXY administration on physical performance in HH. Research 1. Cardiorespiratory responses to physical exercise are expected to meet the organism's metabolic demands. As carotid body (CB) glomus cells have been proposed as metabolic sensors, we sought to determine their contribution to peak oxygen uptake (VO2peak) during exercise in rats. Adult male Wistar Kyoto rats underwent bilateral co-injection of two adeno-associated viruses (AAVs) at the CB bifurcation (AVV-TH-Cre-SV40 and AVV-hSyn-DREADD(Gi)-mCherry). Clozapine-N-oxide (1 mg/kg, i.p.) was administered to activate the inhibitory DREADD-Gi receptor and suppress CB chemosensory activity. Three weeks after AVV infection we evaluated ventilatory and CB chemosensory responses to sodium cyanide (NaCN), the hypobaric-hypoxic ventilatory response (HHVR), lactate-dependent ventilatory response, arterial blood pressure, exercise performance and VO2peak. Chemogenetic inhibition of CB glomus cells reduced resting oxygen consumption and ventilatory responses to lactate. In anaesthetized rats acute chemogenetic inhibition of glomus cells markedly diminished the CB chemosensory and ventilatory responses elicited by NaCN, as well as lactate-dependent hyperventilation after CB resection. Similarly HHVR was markedly reduced in non-anaesthetized animals. Notably chemogenetic inhibition of CB glomus cells significantly reduced VO2peak without altering the time required to reach it. These findings support a novel role for CB glomus cells as metabolic sensors that influence VO2peak during maximal physical exertion, independent of overall exercise performance. KEY POINTS: Carotid body (CB) glomus cells may function as sensors of metabolic activity through the release of lactate from muscle and its accumulation during physical exertion. CB type I chemoreceptor cells are necessary and play a crucial role in sensing metabolism at rest and during exertion. The CB acts as a metabolic sensor that triggers metabolism during physical exertion, mediating the increment of peak O2 uptake during exertion, without affecting exercise performance. Research 2. Outstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats. A vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO2: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups. The findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH. Together, these findings demonstrate the dual influence of CB chemosensory signaling and oxytocinergic modulation on oxygen consumption, vagal control, and exercise capacity under normoxic and hypoxic conditions, offering new insights into the physiological adaptations required for optimal performance during environmental stress.