Chemogenetic inhibition of the carotid bodies blunts hind-limb suspension microgravity-induced muscle alterations in rats

Microgravity is known to promote muscle loss and impair physical performance. The carotid body (CB) chemoreceptors are sensitive to several stimuli and have been associated with peripheral vascular control and deterioration in exercise performance. Accordingly, it is plausible that the CB chemoreflex drive may modify the microgravity-induced muscle changes and, consequently, exercise performance. Thus, it is reasonable to propose that a microgravity environment can alter the CB chemoreflex drive, affecting exercise performance. Hence, we aimed to determine the effects of simulated microgravity, through the hind-limb suspension model, on hypoxic ventilatory chemoreflex drive and to examine whether modulation of the CB chemoreflex function influences exercise performance. Adult male Wistar Kyoto rats underwent hind-limb suspension (HLS; <i>n</i> = 6) or the sham condition (<i>n</i> = 4) for 2 wk. A separate group of rats received bilateral injection of two adeno-associated viruses in the CB bifurcation (AVV-TH-Cre-SV40 and AVV-hSyn-DREADD(Gi)-mCherry) (HLS + CB-G_i, <i>n</i> = 4) to partially inhibit the CB chemosensory responses. Clozapine-<i>N</i>-oxide (1 mg/kg/day) was administered via osmotic minipump to activate the inhibitory DREADD-Gi receptor. Before and after exposure to HLS, we measured the hypobaric-hypoxic ventilatory response (HHVR), muscle performance, and V̇o_2peak. HLS promotes a significant increase in HHVR and a decrease in body weight, back leg muscle strength, soleus mass, and V̇o_2peak. Notably, CB inhibition reduced the HLS-induced deterioration in muscle mass and strength, as well as body weight loss. Our findings suggest a novel role for CB chemoreceptors in mediating the decline in muscle strength induced by HLS, reduced muscle mass, and body weight loss.<b>NEW & NOTEWORTHY</b> This study reveals that carotid body (CB) chemoreceptors contribute to muscle dysfunction induced by simulated microgravity. In rats, hind-limb suspension increased hypoxic ventilatory drive and impaired muscle strength, mass, and V̇o_2peak. Inhibiting CB chemosensory activity significantly attenuated these effects. These findings identify a novel physiological role for CBs in mediating microgravity-induced muscle decline, suggesting that the CB chemoreflex may be a potential target for preserving physical performance during spaceflight or similar conditions.