Janes Tara A, Ambrozio-Marques Danuzia, Fournier Sébastien, Joseph Vincent, Soliz Jorge, Kinkead Richard
Department of Physiology, Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.
Department of Pediatrics, Québec Heart and Lung Institute, Université Laval, Québec, QC, Canada.
Front Physiol. 2021 Dec 24;12:781662. doi: 10.3389/fphys.2021.781662. eCollection 2021.
Excessive carotid body responsiveness to O and/or CO/H stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone supplementation may increase the risk of sleep-disordered breathing; however, the site of action is unknown. The present study tested the hypothesis that testosterone supplementation potentiates carotid body responsiveness to hypoxia in adult male rats. Because testosterone levels decline with age, we also determined whether these effects were age-dependent. hybridization determined that androgen receptor mRNA was present in the carotid bodies and caudal nucleus of the solitary tract of adult (69 days old) and aging (193-206 days old) male rats. In urethane-anesthetized rats injected with testosterone propionate (2 mg/kg; i.p.), peak breathing frequency measured during hypoxia (FiO = 0.12) was 11% greater vs. the vehicle treatment group. Interestingly, response intensity following testosterone treatment was positively correlated with animal age. Exposing carotid body preparations from young and aging rats to testosterone (5 nM, free testosterone) 90-120 min prior to testing showed that the carotid sinus nerve firing rate during hypoxia (5% CO + 95% N; 15 min) was augmented in both age groups as compared to vehicle (<0.001% DMSO). Ventilatory measurements performed using whole body plethysmography revealed that testosterone supplementation (2 mg/kg; i.p.) 2 h prior reduced apnea frequency during sleep. We conclude that in healthy rats, age-dependent potentiation of the carotid body's response to hypoxia by acute testosterone supplementation does not favor the occurrence of apneas but rather appears to stabilize breathing during sleep.
颈动脉体对氧气和/或二氧化碳/氢离子刺激反应过度会导致睡眠期间呼吸不稳定和呼吸暂停。在性腺功能减退的男性中，补充睾酮可能会增加睡眠呼吸障碍的风险；然而，作用部位尚不清楚。本研究检验了以下假设：补充睾酮会增强成年雄性大鼠颈动脉体对低氧的反应性。由于睾酮水平会随着年龄下降，我们还确定了这些影响是否与年龄有关。杂交检测确定，成年（69日龄）和老龄（193 - 206日龄）雄性大鼠的颈动脉体和孤束尾核中存在雄激素受体mRNA。在注射丙酸睾酮（2 mg/kg；腹腔注射）的乌拉坦麻醉大鼠中，低氧（吸入氧分数 = 0.12）期间测得的呼吸频率峰值比溶剂对照组高11%。有趣的是，睾酮治疗后的反应强度与动物年龄呈正相关。在测试前90 - 120分钟，将年轻和老龄大鼠的颈动脉体标本暴露于睾酮（5 nM，游离睾酮）中，结果显示，与溶剂（<0.001%二甲亚砜）相比，两个年龄组在低氧（5%二氧化碳 + 95%氮气；15分钟）期间颈动脉窦神经放电频率均增加。使用全身体积描记法进行的通气测量显示，提前2小时腹腔注射补充睾酮（2 mg/kg）可降低睡眠期间的呼吸暂停频率。我们得出结论，在健康大鼠中，急性补充睾酮对颈动脉体低氧反应的年龄依赖性增强并不利于呼吸暂停的发生，反而似乎能稳定睡眠期间的呼吸。
