The carotid body mediates peak oxygen uptake during maximal physical exertion in rats

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 ( ${\dot{V}}_{O_2\mathrm{peak}}$ ) 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 ${\dot{V}}_{O_2\mathrm{peak}}$ . 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 ${\dot{V}}_{O_2\mathrm{peak}}$ without altering the time required to reach it. These findings support a novel role for CB glomus cells as metabolic sensors that influence ${\dot{V}}_{O_2\mathrm{peak}}$ 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.