Dynamic ventilatory responses in rats: normal development and effects of prenatal nicotine exposure.
Infants of smoking mothers are at increased risk of SIDS, one cause of which is thought to be due to impaired ventilatory responses. We tested the hypotheses that prenatal nicotine exposure impairs the development of dynamic carotid chemoreceptor-driven ventilatory responses, and reduces the ability to lower metabolic rate in hypoxia. Osmotic minipumps were implanted into 20 pregnant rats at day 3 of gestation to deliver nicotine (6 mg/kg per day free base) or saline for 4 weeks. Minute ventilation was recorded breath by breath in rat pups at 3, 8 and 18 days (n = 6, 8 and 6) postnatal in response to 5-sec challenges of 100% O2 (Dejours test) and 5% O2 + 5% CO2. Carotid sinus nerve (CSN) responses to hypoxia and CO2 were recorded from 22 control and 17 nicotine-exposed preparations at ages between 3-20 days. Oxygen consumption (V(O)2) was measured in groups of pups at 3 days (n = 7 each for nicotine and control) and 8 days (n = 5 each for nicotine and control) in room air and 10% O2. There was no detectable effect of nicotine exposure on the development of CSN responses. Ventilatory responses to 5% O2-5% CO2 increased with age but did not differ between nicotine and control groups. Ventilatory responses to 100% O2 were unaffected by nicotine exposure at 8 and 18 days. However, the 3-day nicotine group showed no significant response to 100% O2 whereas V(E) was significantly reduced in the control group by 100% O2. There was no significant effect of nicotine exposure on the ability to reduce oxygen consumption in hypoxia at 3 or 8 days, but at 3 days, baseline (room air) variability in oxygen consumption was greater in the nicotine group. We conclude that nicotine exposure appears to result in abnormal ventilatory responses to withdrawal of baseline peripheral chemoreceptor drive during a period of early postnatal life. We speculate that a transient abnormality could contribute to a period of instability and increased vulnerability to challenges.
Bamford
O S
OS
The Johns Hopkins Pediatric Sleep and Breathing Disorders Center, Johns Hopkins Childrens Center, Baltimore, MD 21287, USA. obamford@welchlink.welch.jhu.edu
Carroll
J L
JL
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D002346:Carotid Sinus / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000254:growth & development / Q000502:physiology; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012137:Respiratory System / Q000187:drug effects / Q000254:growth & development*; D012307:Risk Factors; D013398:Sudden Infant Death
D018722:Nicotinic Agonists; D002245:Carbon Dioxide; D009538:Nicotine