title: Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street Northwest, Ross Hall 640, Washington, DC 20037, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Woerman
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D004242:Diving; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex; D013458:Sulfur Dioxide / Q000633:toxicity*; D009435:Synaptic Transmission / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D013458:Sulfur Dioxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: Autonomic nervous system; Electrophysiology; Neurotransmitters; Parasympathetic; Tachycardia