Perinatal Nicotine Exposure Increases Angiotensin II Receptor-Mediated Vascular Contractility in Adult Offspring

Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring. AIMS: The 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 METHODS: Nicotine 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 FINDINGS: Nicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC(20)-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 [Ca(2+)](i) concentrations but dependent on Ca(2+) sensitivity. Perinatal nicotine treatment significantly enhanced vascular ATR type 1a (AT(1a)R) but not AT(1b)R mRNA levels in adult rat offspring, which was associated with selective decreases in DNA methylation at AT(1a)R promoter. Contrast to the effect on AT(1a)R, nicotine decreased the mRNA levels of vascular AT(2)R gene, which was associated with selective increases in DNA methylation at AT(2)R promoter. SIGNIFICANCE: Our results indicated that perinatal nicotine exposure caused an epigenetic programming of vascular ATRs and their-mediated signaling pathways, and suggested that differential regulation of AT(1)R/AT(2)R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood.