Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: implications for sudden infant death syndrome.
Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.
Neff
Robert A
RA
Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA. phmdxm@gwumc.edu
Simmens
Samuel J
SJ
Evans
Cory
C
Mendelowitz
David
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000294:innervation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007223:Infant; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D013398:Sudden Infant Death; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D005998:Glycine