Alterations in cholinergic sensitivity of respiratory neurons induced by pre-natal nicotine: a mechanism for respiratory dysfunction in neonatal mice.
Nicotine may link cigarette smoking during pregnancy with sudden infant death syndrome (SIDS). Pre-natal nicotine leads to diminished ventilatory responses to hypercarbia and reduced central chemoreception in mice at post-natal days 0-3. We studied how pre-natal nicotine exposure changes the cholinergic contribution to central respiratory chemoreception in neonatal isolated brainstem-spinal cord and slice preparations. Osmotic minipumps, implanted subcutaneously into 5-7 days pregnant mice, delivered saline or nicotine ditartrate 60 mg kg(-1) d(-1) for up to 28 days. In control preparations, acidification of the superfusion medium from pH 7.4 to 7.3 increased the frequency and reduced the amplitude of fictive respiration. In nicotine-exposed neonatal mice, the reduction in amplitude induced by acidification was reduced. In control preparations, atropine suppressed respiratory responses to acidification, while hexamethonium did not. By contrast, in nicotine-exposed preparations, hexamethonium blocked chemosensory responses but atropine did not. Our results indicate that pre-natal nicotine exposure switches cholinergic mechanisms of central chemosensory responses from muscarinic receptors to nicotinic receptors. Modification of the cholinergic contribution to central chemoreception may produce respiratory dysfunctions, as suggested by receptor-binding studies in victims of SIDS.
Coddou
Claudio
C
Faculty of Chemistry and Biology, Department of Biology, Universidad de Santiago, USACH, Chile, Casilla 40, Correo 33, Santiago, Chile.
Bravo
Eduardo
E
Eugenín
Jaime
J
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D001933:Brain Stem / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D018738:Hexamethonium / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects*
D011950:Receptors, Cholinergic; D018738:Hexamethonium; D009538:Nicotine; D001285:Atropine