Prenatal nicotine exposure recruits an excitatory pathway to brainstem parasympathetic cardioinhibitory neurons during hypoxia/hypercapnia in the rat: implications for sudden infant death syndrome.
Maternal cigarette smoking and prenatal nicotine exposure increase the risk for sudden infant death syndrome (SIDS) by 2- to 4-fold, yet despite adverse publicity, nearly one of four pregnant women smoke tobacco. Infants who succumb to SIDS typically experience a severe bradycardia that precedes or is accompanied by centrally mediated life-threatening apneas and gasping. Although the causes of the apnea and bradycardia prevalent in SIDS victims are unknown, it has been hypothesized that these fatal events are exaggerated cardiorespiratory responses to hypoxia or hypercapnia. Changes in heart rate are primarily determined by the activity of cardiac vagal neurons (CVNs) in the brainstem. In this study, we tested whether hypoxia/hypercapnia evokes synaptic pathways to CVNs and whether these cardiorespiratory interactions are altered by prenatal exposure to nicotine. Spontaneous rhythmic inspiratory-related activity was recorded from the hypoglossal rootlet of 700- to 800-microm medullary sections. CVNs were identified in this preparation by retrograde fluorescent labeling, and excitatory synaptic inputs to CVNs were isolated and studied using patch-clamp electrophysiologic techniques. Hypoxia/hypercapnia did not elicit an increase in excitatory neurotransmission to CVNs in unexposed animals, but in animals that were exposed to nicotine in the prenatal period, hypoxia/hypercapnia recruited an excitatory neurotransmission to CVNs. This study establishes a likely neurochemical mechanism for the exaggerated decrease in heart rate in response to hypoxia/hypercapnia that occurs in SIDS victims.
Huang
Zheng-Gui
ZG
Department of Pharmacology and Physiology, The George Washington University, Washington DC 20037, USA.
Wang
Xin
X
Dergacheva
Olga
O
Mendelowitz
David
D
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009538:Nicotine / Q000008:administration & dosage*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013398:Sudden Infant Death
D009538:Nicotine