The effect of fetal and neonatal nicotine exposure on renal development of AT(1) and AT(2) receptors

Perinatal Biology Center, Soochow University School of Medicine, Suzhou, People's Republic of China.
Reproductive Toxicology (Impact Factor: 3.23). 05/2009; 27(2):149-54. DOI: 10.1016/j.reprotox.2009.01.012
Source: PubMed


Maternal cigarette smoking accompanied with fetal and neonatal growth restriction causes abnormalities in organ development in the postnatal life. The present study determined the effect of maternal administration of nicotine on the development of the kidney in rats by examining the expression of renal angiotensin II receptors at mRNA and protein levels as well as kidney weight during postnatal development.
Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Kidneys were removed and collected from both male and female offspring at ages of 14-day-old, 30-day-old, and 5-month-old. Maternal nicotine administration significantly reduced renal AT(2) receptor (AT(2)R) mRNA and protein abundance in both males and females at all three developmental ages examined.
Although AT(1) receptor (AT(1)R) mRNA and protein levels were not significantly changed between the control offspring and the offspring exposed to maternal nicotine during the early developmental period, the renal AT(1)R/AT(2)R ratio was significantly increased. This was associated with a significant decrease of kidney weight in both male and female offspring.
The results demonstrated that the development of renal angiotensin II receptor could be changed following exposure to perinatal nicotine, and such change in the kidney could be long-term in postnatal life.

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    • "Our recent studies have demonstrated that perinatal nicotine exposure enhances AT1R but decreases AT2R protein levels in the vasculatures, resulting in a significant increased vascular reactivity and elevated BP response to Ang II in adult offspring [9]. Furthermore, previous studies have demonstrated that fetal nicotine exposure impairs kidney development and reprograms renal ATR expression which may contribute to fetal programming of hypertension [19], [20]. These studies suggest that the programming of Ang II receptor-mediated signaling pathways is a mechanistic link between programmed cardiovascular dysfunction and intrauterine adverse factors during early development. "
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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.
    PLoS ONE 09/2014; 9(9):e108161. DOI:10.1371/journal.pone.0108161 · 3.23 Impact Factor
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    • "Maternal nicotine increased collagen reaction in lung parenchyma and caused abnormal bronchogenesis in bronchopulmonary development (5). Nicotine causes developmental defects and weight loss in organs such as kidneys and reduces their angiotensin receptors (6). A recent investigation has demonstrated that nicotine enhances renal diseases and increases the rate of oxidative stress in mice (7). "
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    ABSTRACT: Background:Maternal cigarette smoking causes health risks and developmental defects in the offspring. So far, many studies have been conducted to suppress the effects of nicotine. However, the effects of coadministration of vitamin C and nicotine on extracellular matrix have not gained enough attention.Objectives:This study decided to investigate the effects of vitamin C on fibronectin expression in kidneys of mice offspring, treated with nicotine.Materials and Methods:Eighteen female pregnant BALB/c mice were selected; six mice in the experimental group 1 (exp 1) received nicotine (3 mg/kg/day), six mice in the experimental group 2 (exp 2) received 3 mg/kg/day nicotine and 9 mg/kg/day vitamin C simultaneously, and six were used as the control group and received 3 mL/kg/day normal saline via intraperitoneal (IP) injection parallel to other groups, since the 6th day of gestation to the end of prenatal period. In the first days of delivery, fibronectin content of neonatal kidneys was studied by immunohistochemistry (IHC) assay and gene expression was studied by the real-time PCR.Results:IHC results showed that fibronectin reaction significantly increased in proximal convoluted tubules of exp 1 compared with the control offspring; on the other hand, fibronectin reaction decreased in the mice offspring of exp 2. Gene expression results showed that fibronectin expression in the exp 1 offspring significantly increased compared with the control ones and fibronectin expression decreased in the mice offspring of exp 2.Conclusions:This study revealed that vitamin C could reduce the fibronectin accumulation effects of nicotine on kidney.
    07/2014; 16(7):e17056. DOI:10.5812/ircmj.17056
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    • "However in adult offspring, the kidney weight was not significantly different between the control and hypoxic-treated animals in both females and males. Interesting, perinatal nicotine exposure affected the kidney weight not just in the fetus and neonate but also in female and male adult offspring 21. The finding that the kidney-to-body weight ratio was significantly greater in P7 rats than that in E21 rats indicates a continuous growth and maturation of the kidney in neonatal rats. "
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    ABSTRACT: AIMS: The present study tested the hypothesis that fetal hypoxia adversely affects kidney development in fetal and offspring rats and alter the expression patterns of angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. METHODS: Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 last period of gestation) groups. Protein expression, in the offspring, was determined using western blot. RESULTS: Hypoxic treatment significantly decreased body and kidney weight in 21-day fetuses (E21) and 7-day neonates (P7). In 3-month-old offspring there were no significant differences in body and kidney weight between hypoxic and control animals. Fetal hypoxia had no effect on kidney AT1R density in E21 or P7, but significantly decreased kidney AT1R protein and mRNA abundance in both male and female adults. In contrast, kidney AT2R density was not affected by fetal hypoxia throughout the developmental stages studied. The hypoxia-mediated reduction of nephron numbers was progressively from P7 worsened into the adulthood with females affected more than males. CONCLUSION: The results suggest that fetal hypoxia causes programming of aberrant kidney development and accelerates the aging process of the kidney during the postnatal development, which may contribute to an increased risk of cardiovascular disease.
    International journal of medical sciences 03/2013; 10(5):532-538. DOI:10.7150/ijms.5566 · 2.00 Impact Factor
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