Article

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring

Institute of Pathology, Univ. of Heidelberg, Germany.
AJP Renal Physiology (Impact Factor: 4.42). 05/2011; 301(2):F344-54. DOI: 10.1152/ajprenal.00626.2010
Source: PubMed

ABSTRACT In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

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    • "Although adaptive response to salt during pregnancy is also important for offspring [30], it is not exactly clear how other functional systems may be disturbed from this salt diet. Reduction in number of glomeruli and higher risk of hypertension may occur in offspring from mothers who were subjected to high-salt diet during pregnancy [31]. High-salt intake during pregnancy was investigated in other studies, indicating that cardiac cell and RAS may be disturbed in offspring [32, 33], but gender difference is not exactly known. "
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    ABSTRACT: Introduction. Rennin-angiotensin system and salt diet play important roles in blood pressure control. We hypothesized that the high-salt intake during pregnancy influences the degree of angiotensin-dependent control of the blood pressure in adult offspring. Methods. Female Wistar rats in two groups (A and B) were subjected to drink tap and salt water, respectively, during pregnancy. The offspring were divided into four groups as male and female offspring from group A (groups 1 and 2) and from group B (groups 3 and 4). In anesthetized matured offspring mean arterial pressure (MAP), heart rate and urine output were measured in response to angiotensin II (AngII) (0-1000 ng/kg/min, iv) infusion. Results. An increase in MAP was detected in mothers with salt drinking water (P < 0.05). The body weight increased and kidney weight decreased significantly in male offspring from group 3 in comparison to group 1 (P < 0.05). MAP and urine volume in response to AngII infusion increased in group 3 (P < 0.05). These findings were not observed in female rats. Conclusion. Salt overloading during pregnancy had long-term effects on kidney weight and increased sex-dependent response to AngII infusion in offspring (adult) that may reveal the important role of diet during pregnancy in AngII receptors.
    International journal of vascular medicine 04/2014; 2014(3, part 2):876527. DOI:10.1155/2014/876527
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    • "Development and structure of the fetal/offspring kidney has been previously suggested to be affected by maternal high salt diet but the data are conflicting, with some groups showing a decrease in, for example, nephron number [34] while others report no change [35], [36]. In this study, we found no in vivo evidence to support a marked effect of maternal salt diet on offspring kidney anatomy and physiology; nephron numbers in near-term offspring (i.e. during nephrogenesis) and in adulthood (i.e. after completion of nephrogenesis) were similar between groups. "
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    ABSTRACT: Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young.
    PLoS ONE 08/2013; 8(8):e72682. DOI:10.1371/journal.pone.0072682 · 3.23 Impact Factor
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    • "Increased maternal salt intake can result in renal structural and functional changes similar to those produced by gestational protein restriction [70, 71]. Both excessively high and low maternal sodium intakes during pregnancy in the rat cause aberrant expression of genes critical for normal metanephric organogenesis and reduce the final number of glomeruli in the offspring, predisposing to hypertension later in life [76, 120]. Occurrence of renal hypodysplasia caused by high maternal salt intake during gestation in bradykinin B2 receptor-deficient mice provides proof of the principle that environmental factors may act in concert with single-gene mutations to cause aberrant kidney development [121]. "
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    ABSTRACT: A growing body of evidence supports the concept that changes in the intrauterine milieu during "sensitive" periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as "developmental programming" or "developmental origins of health and disease." The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500 g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencing in utero environment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD.
    International Journal of Nephrology 11/2012; 2012(4):760580. DOI:10.1155/2012/760580
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