Effect of prenatal nicotine exposure on biphasic hypoxic ventilatory response and protein kinase C expression in caudal brain stem of developing rats

J Appl Physiol (1985). 2004 Jun;96(6):2213-9. doi: 10.1152/japplphysiol.00935.2003. Epub 2004 Jan 29.


Current evidence suggests that maternal smoking is associated with decreased respiratory drive and blunted hypoxic ventilatory response (HVR) in the newborn. The effect of prenatal nicotine exposure on overall changes in HVR has been studied; however, there is limited data on the effect of nicotine exposure on each component of biphasic HVR. To examine this issue, 5-day timed-pregnant Sprague-Dawley rats underwent surgical implantation of an osmotic minipump containing either normal saline (Con) or a solution of nicotine tartrate (Nic) to continuously deliver free nicotine at 6 mg.kg of maternal weight(-1).day(-1). Rat pups at postnatal days 5, 10, 15, and 20 underwent hypoxic challenges with 10% O(2) for 20 min using whole body plethysmography. At postnatal day 5, Nic was associated with attenuation of peak HVR; peak minute ventilaton increased 44.0 +/- 6.8% (SE) from baseline in Nic pups, whereas that of Con pups increased 62.9 +/- 5.1% (P < 0.05). Nic pups also had a reduction in the magnitude of ventilatory roll-off; minute ventilation at 15 min decreased 7.3 +/- 7.1% in Nic pups compared with 27.3 +/- 4.0% in Con pups (P < 0.05). No significant difference in HVR was noted at postnatal days 10, 15, and 20. Hypercapnic response was similar at all ages. We further investigated the effect of prenatal nicotine exposure on PKC expression in the caudal brain stem (CB) of developing rats. At postnatal day 5, Nic was associated with increased expression of PKC-beta and PKC-delta in CB, whereas other PKC isoforms were not affected. It is concluded that prenatal nicotine exposure is associated with modulation of biphasic HVR and a selective increase in the expression of PKC-beta and PKC-delta within the CB of developing rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Female
  • Hypoxia / chemically induced*
  • Hypoxia / physiopathology
  • Isoenzymes / metabolism
  • Nicotine / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mechanics / drug effects
  • Respiratory Mechanics / physiology*


  • Isoenzymes
  • Nicotine
  • Protein Kinase C