Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, SP, Brazil.
Sleep. 2023 May 10;46(5). doi: 10.1093/sleep/zsad055.
Exposure to postnatal chronic intermittent hypoxia (pCIH), as experienced in sleep-disordered breathing, is a risk factor for developing cardiorespiratory diseases in adulthood. pCIH causes respiratory instability and motor dysfunction that persist until adult life. In this study, we investigated the impact of pCIH on the sympathetic control of arterial pressure in rats.
Neonate male Holtzman rats (P0-1) were exposed to pCIH (6% O2 for 30 seconds, every 10 minutes, 8 h/day) during their first 10-15 days of life, while control animals were maintained under normoxia. In early adult life (P25-40), freely behaving pCIH animals (n = 13) showed higher baseline arterial pressure levels linked to augmented sympathetic-mediated variability than control animals (n = 12, p < 0.05). Using decerebrated in situ preparations, we found that juvenile pCIH rats exhibited a twofold increase in thoracic sympathetic nerve activity (n = 14) and elevated firing frequency of ventromedullary presympathetic neurons (n = 7) compared to control rats (n = 6-7, p < 0.05). This pCIH-induced sympathetic dysregulation was associated with increased HIF-1α (hypoxia-inducible factor 1 alpha) mRNA expression in catecholaminergic presympathetic neurons (n = 5, p < 0.05). At older age (P90-99), pCIH rats displayed higher arterial pressure levels and larger depressor responses to ganglionic blockade (n = 6-8, p < 0.05), confirming the sympathetic overactivity state.
pCIH facilitates the vasoconstrictor sympathetic drive by mechanisms associated with enhanced firing activity and HIF-1α expression in ventromedullary presympathetic neurons. This excessive sympathetic activity persists until adulthood resulting in high blood pressure levels and variability, which contribute to developing cardiovascular diseases.
在睡眠呼吸障碍中经历的产后慢性间歇性低氧（pCIH）暴露是成年后发生心肺疾病的危险因素。pCIH 导致呼吸不稳定和运动功能障碍，这种情况持续到成年期。在这项研究中，我们研究了 pCIH 对大鼠动脉压力交感控制的影响。
新生雄性霍兹曼大鼠（P0-1）在生命的前 10-15 天接受 pCIH（6%O2 30 秒，每 10 分钟一次，每天 8 小时），而对照动物则在常氧下维持。在早期成年期（P25-40），自由活动的 pCIH 动物（n=13）表现出更高的基础动脉压水平，与对照组动物相比，交感介导的变异性增加（n=12，p<0.05）。使用去大脑原位制备物，我们发现幼年 pCIH 大鼠的胸交感神经活性增加了两倍（n=14），腹侧延髓节前交感神经元的放电频率升高（n=7）与对照组大鼠（n=6-7，p<0.05）。这种 pCIH 诱导的交感神经失调与儿茶酚胺能节前交感神经元中 HIF-1α（缺氧诱导因子 1α）mRNA 表达增加有关（n=5，p<0.05）。在老年时（P90-99），pCIH 大鼠显示出更高的动脉压水平和更大的降压反应对神经节阻滞（n=6-8，p<0.05），证实了交感神经过度活跃的状态。
pCIH 通过与腹侧延髓节前交感神经元中放电活动增强和 HIF-1α 表达相关的机制促进血管收缩性交感驱动。这种过度的交感活动持续到成年期，导致高血压水平和变异性增加，这有助于发展心血管疾病。
