Impaired lung mitochondrial oxidative capacity following perinatal nicotine exposure in rats (1159.2)

Abstract

Perinatal smoke and nicotine exposure predisposes to chronic lung disease and morbidity. As the PPARγ pathway is implicated in structural and functional airway deficits in a well‐established rat model of perinatal nicotine exposure, mitochondrial derangement may accompany these deficits. Therefore, we hypothesized that perinatal nicotine exposure would result in lung mitochondrial dysfunction.Sprague‐Dawley dams received either placebo (CON) or nicotine (NIC, 1 mg.kg‐1) daily from embryonic day 6 to postnatal day 21. Postpartum, pups were breast feed ad libitum. Parenchymal lung sections (~10mg) were taken from adult males for mitochondrial assessment in situ (O2K, Oroboros).Body mass was not different at 5 months between CON and NIC (637±65 vs. 624±49 g; p=0.71). ADP‐stimulated O2 consumption (JO2) was ~50% less in NIC (n=6) compared to CON (n=6) (4.5±0.8 vs.8.8±2.5 pmol.s.mg‐1, respectively; p<0.05). Uncoupled JO2 was ~60% less in NIC (6.4±1.5 vs. 15.4±5.7 pmol.s.mg‐1; p<0.05), each with excess complex IV capacity. Flux control ratios were not different between conditions (p>0.05).These data suggest reduced mitochondrial density, rather than respiratory chain complex dysfunction, with perinatal nicotine exposure. Low maximal JO2 with nicotine exposure, possibly via suppressed mitochondrial biogenesis, may predispose towards increased oxidative stress and chronic lung disease.Grant Funding Source: Supported by NIH HD51857, HD71731