The effect of prenatal nicotine exposure on biphasic hypoxic ventilatory response and protein kinase C (PKC) expression in caudal brainstem of developing rats

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, 5day 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/day. Rat pups at postnatal day 5(P5), 10(P10), 15(P15) and 20(P20) underwent hypoxic challenges with 10% O2 for 20 minutes using whole body plethysmography. At P5, Nic was associated with attenuation of peak HVR; peak VE increased 44.0±6.8 % [SE] from baseline in Nic pups while that of Con pups increased 62.9± 5.1 % (P<0.05). Nic pups also had reduction in the magnitude of ventilatory roll-off ; VE at 15 minutes decreased 7.3±7.1 % in Nic pups as compared to 27.3±4.0 % in Con pups (P<0.05). No significant difference in HVR was noted at P10, P15 and P20. Hypercapnic response was similar at all ages. We further investigated the effect of prenatal nicotine exposure on PKC expression in caudal brainstem (CB) of developing rats. At P5, Nic was associated with increased expression of PKCand PKCin CB while other PKC isoforms were not affected. It is concluded that prenatal nicotine exposure is associated with modulation of biphasic HVR and selective increase in the expression of PKCand PKCwithin the CB of developing rats.