title: Perinatal nicotine exposure increases angiotensin II receptor-mediated vascular contractility in adult offspring.
abstract: Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  Nicotine 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.
  
  
  CONCLUSIONS
  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 AT1R/AT2R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood.
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: DaLiao
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Dasgupta
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000502:physiology*; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D009119:Muscle Contraction; D018994:Myosin Light Chains / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D018994:Myosin Light Chains; D011945:Receptors, Angiotensin; D009538:Nicotine