Role of raphe magnus 5-HT1A receptor in increased ventilatory responses induced by intermittent hypoxia in rats

• Published in: Respiratory research 2022-03, Vol.23 (1), p.42-42, Article 42
• Main Authors: Su, Jiao, Meng, Yang, Fang, Yifei, Sun, Linge, Wang, Mengge, Liu, Yanjun, Zhao, Chunling, Dai, Liping, Ouyang, Songyun
• Format: Article
• Language: English
• Subjects: 5-HT1A receptor; Complications and side effects; Genetic aspects; Health aspects; Hypoxia; Intermittent hypoxia; Patient outcomes; Physiological aspects; Raphe magnus nucleus; Smad proteins; Ventilation
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-022-01970-6

Background Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT.sub.1A) receptor on the increased ventilatory responses induced by intermittent hypoxia. Methods Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT.sub.1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia. Results Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT.sub.1A receptor in the RMg region alleviated this phenomenon. Conclusions The results indicate that RMg 5-HT.sub.1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia. Keywords: Intermittent hypoxia, Ventilation, Raphe magnus nucleus, 5-HT.sub.1A receptor