The effect of fetal and neonatal nicotine exposure on renal development of AT(1) and AT(2) receptors.
ABSTRACT 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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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 · 3.53 Impact Factor
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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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ABSTRACT: Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programming of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin-angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programming of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.Neuroscience & Biobehavioral Reviews 12/2014; 51. DOI:10.1016/j.neubiorev.2014.12.012 · 10.28 Impact Factor