Influence of prenatal nicotine exposure on development of ventilatory responses to hypoxia and asphyxia.

Abstract

Ventilatory responses to 3 minutes of hypoxia (16, 12 and 10 % inspired O2, balance N2), asphyxia (12% O2, 5% CO2, balance N2) and normoxia were studied in neonatal rats that were exposed to either nicotine (nicotine tartrate, 6 mg/kg/day) or saline in the prenatal period. Measurements were obtained on postnatal days (P) 3, 6, 9, 12 and 18, using head-out body plethysmography. Plethysmograph temperature was servocontrolled within the thermoneutral zone for neonatal rats (33 +/− 0.1 degrees C). Normoxic pulmonary ventilation (VI) increased progressively as the animals grew, with no between-group differences at any age. With 16% O2, nicotine-exposed rats had a lower VI than saline-exposed rats on P9, and a higher VI on P18. In response to 12% O2, nicotine-exposed rats had a higher VI on P12. With 10% O2, VI was lower in nicotine-exposed rats on P3, but higher on P12 and P18. Prenatal nicotine exposure did not alter the response to asphyxia with the exception of a reduced response on the 9th day of life. The increase in body mass with age was similar in both groups, with the exception of a slightly higher weight in nicotine-exposed animals on P18. Prenatal nicotine exposure causes complex developmental changes in hypoxic sensitivity, expressed as attenuation over the first 9 days of life, and facilitation on days 12–18. The developmental switch between P9-P12 is consistent with a major readjustment of brainstem neurotransmitter receptor densities near P12 (Liu et al, JAP. 98: 1442, 2005). Support: AHA 0255970Z