Skip to content

Advertisement

Respiratory Research

What do you think about BMC? Take part in

Volume 2 Supplement 1

Neural Control of Breathing

Open Access

Postnatal development of neural chemoafferent pathway and respiration is altered following prenatal nicotine exposure in rats

  • S Malhière2,
  • Y Dalmaz2,
  • D Perrin2,
  • JC Roux2,
  • H Lagercrantz1,
  • JM Pequignot2 and
  • J Peyronnet1, 2
Respiratory Research20012(Suppl 1):P16

https://doi.org/10.1186/rr132

Received: 2 August 2001

Published: 17 August 2001

Maternal smoking during pregnancy increases the risk of Sudden Infant Death. A defect in cardiorespiratory control has been suggested. Chronic exposure to nicotine during fetal development of rat induced postnatal developmental disorders on central neural pathways [1], autonomic function [2], carotid body chemorecep-tors [3], ventilatory response to hyperoxia [4]. The interrelation between all these sparse data has to be investigated. We hypothesized that exposure to nicotine might impair or delay the development of respiratory control pathways, ie, of the carotid body chemoafferent pathway, causing an abnormal response to ventila-tory challenges. On the 5th day of gestation, pregnant Sprague-Dawley rats received a transdermal patch delivering, either 50 mg of nicotine free base over 21 days, or excipient. At birth, male pups were selected and analysed at postnatal day 3, 7, 11, 14, 21 and 68. The in vivo tyrosine hydroxylase activity was determined in offspring carotid bodies and brainstem areas involved in cardiorespi-rarory events (A2C2 in the nucleus tractus solitarius, A1C1 in the ventrolateralmedulla, A5 and A6 in the pons) by measuring the endogenous DOPA accumulation after blockade of DOPA decar-boxylase with NSD (m-hydroxybenzylhydrazine) 100 mg/kg, 20 min. Ventilation was measured in awake pups using a barometric plethysmograph, at rest and in response to 10% hypoxic challenges. The response to hypoxia was recorded at 1, 4, 7 and 10 min of hypoxic exposure. Concerning ventilation, prenatal nicotine induced a significant increase in resting ventilation of the 7-and 11-day-old offspring and an altered response to hypoxic challenge characterised by an instability of the response within the first 2 weeks and an increased amplitude of response. Concerning neu-rochemistry, the tyrosine hydroxylase activity is reduced in brainstem areas (A5, A1C1, A6) until 11 days and the decrease in the TH activity observed in the control carotid body until 7 days of age is delayed until 11 days in the prenatal nicotine offspring. In conclusion, prenatal nicotine altered development of the chemoafferent pathway. The long-lasting hypoxic ventilatory response of neonate type might be in relation with the delay in the carotid body resetting. This could lead to increased vulnerability during the early postnatal life, by reducing the ability to face up to environmental stresses. These data might be relevant for SIDS physiopathology.

Authors’ Affiliations

(1)
Department of Woman and Child Health, Karolinska Institute
(2)
Laboratoire de Physiologie, UMR CNRS 5578

References

  1. Slotkin TA: Nervous System. Academic Press. 1992, 92-124.Google Scholar
  2. Slotkin TA, Epps TA, Stenger ML, Sawyer KJ, Seidler FJ: Cholinergic receptors in heart and brainstem of rats exposed to nicotine during development: implications for hypoxia tolerance and perinatal mortality. Brain Res Dev Brain Res. 1999, 113: 1-12. 10.1016/S0165-3806(98)00173-4.PubMedView ArticleGoogle Scholar
  3. Holgert H, Hokfelt T, Hertzberg T, Lagercrantz H: Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc Natl Acad Sci. 1995, 92: 7575-7579. 10.1073/pnas.92.16.7575.PubMedPubMed CentralView ArticleGoogle Scholar
  4. Bamford OS, Carroll JL: Dynamic ventilatory responses in rats: normal development and effects of prenatal nicotine exposure. Respir Physiol. 1999, 117: 29-40. 10.1016/S0034-5687(99)00054-7.PubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd 2001

Advertisement