Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia
J Neurophysiol. 2015 Jan 1;113(1):380-9. doi: 10.1152/jn.00302.2014. Epub 2014 Oct 15.
Patients with sleep-related disorders, including obstructive sleep apnea (OSA), have an increased risk of cardiovascular diseases. OSA events are more severe in rapid eye movement (REM) sleep. REM sleep further increases the risk of adverse cardiovascular events by diminishing cardioprotective parasympathetic activity. The mechanisms underlying REM sleep-related reduction in parasympathetic activity likely include activation of inhibitory input to cardiac vagal neurons (CVNs) in the brain stem originating from the lateral paragigantocellular nucleus (LPGi), a nucleus that plays a role in REM sleep control. This study tests the hypothesis that chronic intermittent hypoxia and hypercapnia (CIHH), an animal model of OSA, inhibits CVNs because of exaggeration of the GABAergic pathway from the LPGi to CVNs. GABAergic neurotransmission to CVNs evoked by electrical stimulation of the LPGi was examined with whole cell patch-clamp recordings in an in vitro brain slice preparation in rats exposed to CIHH and control rats. GABAergic synaptic events were enhanced after 4-wk CIHH in both male and female rats, to a greater degree in males. Acute hypoxia and hypercapnia (H/H) reversibly diminished the LPGi-evoked GABAergic neurotransmission to CVNs. However, GABAergic synaptic events were enhanced after acute H/H in CIHH male animals. Orexin-A elicited a reversible inhibition of LPGi-evoked GABAergic currents in control animals but evoked no significant changes in CIHH male rats. In conclusion, exaggerated inhibitory neurotransmission from the LPGi to CVNs in CIHH animals would reduce cardioprotective parasympathetic activity and enhance the risk of adverse cardiovascular events.
患有睡眠相关障碍的患者，包括阻塞性睡眠呼吸暂停（OSA），心血管疾病的风险增加。快速眼动（REM）睡眠中的 OSA 事件更为严重。REM 睡眠通过减少心脏保护性副交感神经活动进一步增加不良心血管事件的风险。REM 睡眠相关副交感神经活动减少的潜在机制可能包括来自外侧巨细胞旁核（LPGi）的抑制性传入对心脏迷走神经元（CVN）的激活，LPGi 在 REM 睡眠控制中起作用。这项研究检验了这样一个假设，即慢性间歇性低氧和高碳酸血症（CIHH），一种 OSA 的动物模型，通过 LPGi 到 CVN 的 GABA 能途径的夸大抑制 CVN。通过在暴露于 CIHH 和对照大鼠的体外脑片制备中进行全细胞膜片钳记录，检查了 LPGi 电刺激对 CVN 的 GABA 能神经传递。在雄性和雌性大鼠中，4 周 CIHH 后 GABA 能突触事件增强，在雄性大鼠中更为明显。急性低氧和高碳酸血症（H/H）可逆地减弱了 LPGi 对 CVN 的 GABA 能神经传递。然而，在 CIHH 雄性动物的急性 H/H 后，GABA 能突触事件增强。在对照动物中，食欲素-A 引起 LPGi 诱发的 GABA 电流可逆抑制，但在 CIHH 雄性大鼠中没有引起明显变化。总之，CIHH 动物中来自 LPGi 的过度抑制性神经传递会降低心脏保护性副交感神经活动，并增加不良心血管事件的风险。
