Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street Northwest, Ross Hall 640, Washington, DC 20037, USA.
Cardiovasc Res. 2013 Jul 1;99(1):16-23. doi: 10.1093/cvr/cvt057. Epub 2013 Mar 14.
Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure.
Pregnant Sprague-Dawley dams and their pups were exposed to 5 parts per million SO₂ for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO₂ exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO₂ exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO₂ exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO₂ exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO₂ exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO₂ exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons.
Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO₂-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.
二氧化硫（SO₂）是一种空气污染物，它会阻碍新生儿的发育，并引起不良的心肺健康影响，包括心动过速。在这里，开发了一种动物模型，使我们能够（i）在体内改变心率和（ii）改变控制心率的脑干神经元的活性，从而描述围产期 SO₂暴露后的变化。
用 5ppm 的 SO₂ 对妊娠和产后 6 天的 Sprague-Dawley 孕鼠及其幼崽进行 1 小时的每日暴露。在产后 5 天，通过记录幼崽的心电图来检查围产期 SO₂暴露后基础和潜水反射诱发的心率变化。体外研究采用全细胞膜片钳电生理学技术，在保留舌下神经根记录的虚构吸气活动的制剂中，检查 SO₂ 暴露对疑核内心脏迷走神经神经元的神经传递的变化。围产期 SO₂ 暴露增加了心率，并使迷走神经介导的潜水反射诱发的心率变化迟钝。SO₂ 暴露既没有改变自发性也没有改变吸气相关的抑制性 GABA 能或甘氨酸能神经传递到心脏迷走神经元。然而，兴奋性谷氨酸能神经传递减少了 51.2%。这种兴奋性神经传递的减少是河豚毒素敏感的，表明 SO₂ 暴露损害了与心脏迷走神经元突触的先前谷氨酸能神经元的活性。
对心脏迷走神经元的兴奋性谷氨酸能，但不变的抑制性神经传递减少，为观察到的 SO₂ 诱导的心率升高提供了一种机制，即通过损害脑干对心脏的抑制性副交感神经活性。
