Abstract
OBJECTIVE: This study investigates the role of transient receptor potential vanilloid subtype 1 (TRPV1) in acute hypoxic exercise. METHODS: After acute hypoxia intervention, the mRNA expression levels of TRPV1 and 5-hydroxytryptamine 1 A (5-HT1A) in the prefrontal cortex of rats were detected by real-time quantitative polymerase chain reaction (RT-PCR). Meanwhile, the content of 5-hydroxytryptamine (5-HT) in this area was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Hypoxic conditions significantly reduced the duration of high-load exercise performance in rats, resulting in an earlier onset of fatigue and a pronounced decline in exercise capacity (p < 0.05). Acute hypoxic exercise upregulated the expression of TRPV1, 5-HT, and 5-HT1A in the prefrontal cortex (p < 0.05), which may lead to a decrease in exercise capacity. Pharmacological blockade of TRPV1 and 5-HT1A receptors extended the duration of high-load exercise under hypoxic conditions and improved exercise capacity (p < 0.05). CONCLUSION: Our findings indicate that the upregulation of TRPV1, 5-HT, and 5-HT1A is a key mechanism underlying the decline in exercise performance during acute hypoxia. Pharmacological blockade of these pathways effectively alleviates hypoxia-induced exercise fatigue, suggesting they represent promising therapeutic targets for enhancing performance under hypoxic conditions. SIGNIFICANCE: These findings provide a biological basis for developing nutritional strategies to counteract the initial decline in physical performance experienced by military personnel and adventurers during their ascent to high-altitude environments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13102-025-01523-6.