Perinatal Nicotine Exposure Increases Angiotensin II Receptor-Mediated Vascular Contractility in Adult Offspring |
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Authors: | DaLiao Xiao Chiranjib Dasgupta Yong Li Xiaohui Huang Lubo Zhang |
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Affiliation: | Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.; The University of Manchester, United Kingdom, |
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Abstract: | Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring.AimsThe present study was to determine whether perinatal nicotine exposure causes an epigenetic programming of vascular Angiotensin II receptors (ATRs) and their-mediated signaling pathway leading to heightened vascular contraction in adult offspring.Main methodsNicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. The experiments were conducted at 5 months of age of male offspring.Key FindingsNicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC20-P) levels. In addition, the ratio of Ang II-induced tension/MLC-P was also significantly increased in nicotine-treated group compared with the saline group. Nicotine-mediated enhanced constrictions were not directly dependent on the changes of [Ca2+]i concentrations but dependent on Ca2+ sensitivity. Perinatal nicotine treatment significantly enhanced vascular ATR type 1a (AT1aR) but not AT1bR mRNA levels in adult rat offspring, which was associated with selective decreases in DNA methylation at AT1aR promoter. Contrast to the effect on AT1aR, nicotine decreased the mRNA levels of vascular AT2R gene, which was associated with selective increases in DNA methylation at AT2R promoter.SignificanceOur results indicated that perinatal nicotine exposure caused an epigenetic programming of vascular ATRs and their-mediated signaling pathways, and suggested that differential regulation of AT1R/AT2R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood. |
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