Protective effect of antenatal antioxidant on Nicotine-induced heart ischemia-sensitive phenotype in rat offspring

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Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cepsilon (PKCepsilon) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3beta (GSK3beta) protein expression, it significantly increased the phosphorylation of GSK3beta at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCepsilon gene expression and abrogated increased phosphorylation of GSK3beta. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.




Da Liao, X., Wang, L., Huang, X., Li, Y., Dasgupta, C., & Zhang, L. (2016). Protective effect of antenatal antioxidant on Nicotine-induced heart ischemia-sensitive phenotype in rat offspring. PLoS ONE, 11(2).

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