Influence of Prenatal Nicotine Exposure on Development of the Ventilatory Response to Hypoxia and Hypercapnia in Neonatal Rats

In a recent study (Huang YH et al. Respir Physiol Neurobiol 143: 1-8, 2004), we showed that prenatal nicotine exposure (PNE) increased the frequency of spontaneous apneic events on the first 2 days of life in unanesthetized neonatal rats. Here we test the hypothesis that PNE blunts chemoreceptor reflexes. Ventilatory responses to three levels each of hypoxia (inspired O(2) fraction: 16, 12, and 10%) and hypercapnia (3, 6, and 9% inspired CO(2) fraction, all in 50% O(2), balance N(2)), and one level each of combined hypoxia-hypercapnia (H/H; 12% inspired O(2) fraction/5% inspired CO(2) fraction) and hyperoxia (50% O(2), 50% N(2)) were recorded with head-out plethysmography in neonatal rats exposed to either nicotine (N = 12) or physiological saline (N = 12) in the prenatal period. Recordings were made on postnatal day 1 (P1), P3, P6, P9, P12, and P18, in each animal. The change in ventilation in response to hypoxia was blunted in PNE animals on P1 and P3, but there were no other treatment effects. Hyperoxia significantly depressed ventilation in both groups from P3-P18, but there were no significant treatment effects. The ventilatory response to 3, 6, and 9% inspired CO(2) was significantly blunted in PNE animals at all ages studied, due exclusively to a blunted tidal volume response. PNE also blunted the ventilatory response to H/H at all ages, due primarily to blunting of the tidal volume response. PNE had no significant effect on body mass or metabolic rate, except that PNE animals had a slightly higher mass on P18 and a lower metabolic rate on P1. As shown by others, PNE has small and inconsistent effects on hypoxic ventilatory responses, but here we show that responses to hypercapnia and H/H are consistently blunted by PNE due to a diminished tidal volume response. The combination of reduced hypoxic and hypercapnic sensitivity over the first 3 days of life may define an especially vulnerable developmental period.