Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, PC171


Prenatal nicotine exposure decreases the response to hypercapnia in neonatal mice

Cerpa, V ; Otarola, M ; Llona, I ; Eugenin, J ;

1. P. Universidad Catolica de Chile, Santiago, Chile. 2. Universidad de Santiago de Chile, Santiago, Chile.

The neuronal network that generated the respiratory rhythm receives input from chemoreceptors. Small increases in CO2 put up the respiratory activity, being the contribution of central chemoreceptors bigger than that of peripheral.Failures in chemoreception are involved in catastrophic respiratory dysfunctions as the Sudden Infant Death Syndrome. Smoking habit in pregnant women has been related to infants who die from this syndrome. Since the nicotine is the main teratogen found in tobacco, we were interested in studying the effects of prenatal exposure to nicotine upon ventilation, the ventilatory response to hypercapnia, and the respiratory response to acidic challenge in neonatal mice. At the 5-7 day of pregnancy, CF1 pregnant-mice were anesthetized with ketamine/xylazine 80/10 mg kg-1 i.p. to insert subcutaneously an osmotic micropump ALZET which was delivering saline (controls) or nicotine ditartrate 60 mg Kg-1 day-1 (experimentals). They were maintained in separate cages with food and water ad libitum. Ventilation and its response to hypercapnia were studied in (P0-P8) neonates born from experimental and control mothers using whole-body plethysmography. Neonates in the temperature controlled pletysmographic chamber were allowed to breath air during 2 minutes and then they were exposed to air enriched with 10% CO2 (21% O2, N2-balanced) during 20 minutes. Fictive respiration was studied using the block brainstem spinal cord preparation from neonatal mice. P0-P3 neonates were anesthetized with ether and their CNS were removed, decerebrated, transferred to a recording chamber, and superfused with artificial cerebrospinal fluid gassed with 95% O2 5% CO2, pH 7.4. Fictive respiration was recorded with suction electrodes from the C3-C5 ventral roots. Acidification challenge was done by switching the pH of the superfusion medium from 7.4 to 7.3 or 7.1. Nicotine exposed neonates (P0-P3) showed hypoventilation and a respiratory response to hypercapnia lower than that observed in controls. The biggest difference was observed in P0 (62% decrease in minute ventilation, P=0.004, Mann Withney U-test). No difference was observed in P8. In in vitro experiments, both nicotine exposed and controls showed an increased frequency of fictive respiration (P< 0.001, ANOVA 2-tails). However, the magnitude of the respiratory frequency at the different pH was always lower in the nicotine exposed preparations (p=0.03, ANOVA 2-tails). Our results show that prenatal nicotine exposure produces hypoventilation and decreases the ventilatory response to hypercapnia in neonatal mice. They suggest that the prenatal nicotine exposure likely affects the contribution of central chemoreceptors to the respiratory drive.

Where applicable, experiments conform with Society ethical requirements