Developmental origins of adult hypertension: new insights into the role of the kidney

Vehaskari, V. Matti

doi:10.1007/s00467-006-0353-6

Cited by 31 publications

(26 citation statements)

References 33 publications

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“…When the nephron number is markedly reduced (more than 50%), as observed in patients with severe congenital renal hypoplasia and in experimental studies in which the nephron number is dramatically reduced down to 70% or more, early hypertension is more likely to occur [37,79,80]. When nephron number is moderately decreased hypertension and chronic kidney disease may develop with additional factors such as increased sodium or protein intakes [37,[95][96][97][98].…”

Section: Altered Nephrogenesis and Increased Arterial Blood Pressure mentioning

confidence: 99%

Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues

et al. 2010

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Epidemiological and experimental studies show that the risk of cardiovascular and metabolic diseases at adulthood is inversely related to the weight at birth. Although with less evidence, low birth weight has been suggested to increase the risk of chronic kidney disease (CKD). It is well established that the developmental programming of arterial hypertension and of renal disease involves in particular renal factors, especially nephron endowment, which is reduced in low birth weight and maternal diabetes situations. Experimental studies, especially in rodents, have demonstrated the long-term influence of postnatal nutrition and/or postnatal growth on cardiovascular, metabolic and renal functions, while human data are scarce on this issue. Vascular and renal diseases appear to have a "multihits" origin, with reduced nephron number the initial hit and rapid postnatal growth the second hit. This review addresses the current understanding of the role of the kidney, both as a mechanism and as a target, in the developmental origins of adult disease theory, with a particular focus on the long-term effects of postnatal growth and nutrition.

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Section: Altered Nephrogenesis and Increased Arterial Blood Pressure mentioning

confidence: 99%

Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues

et al. 2010

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“…This suggests that steroid exposure alone is sufficient to reduce GFR in male offspring while an additional insult (prematurity) may be required to alter GFR in females. A "two-hit" hypothesis has been proposed to explain the development of hypertension in response to prenatal programming (52).…”

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confidence: 99%

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Tang¹,

Carey²,

Bi³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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posure to clinically relevant doses of glucocorticoids during fetal life increases blood pressure in adult male and female sheep. The purpose of this study was to evaluate the effects of prenatal exposure to betamethasone at 80 -81 days of gestation on renal function in ewes and rams at 1.5 yr of age. In prenatal betamethasone-exposed males, compared with the vehicle-exposed animals, basal glomerular filtration rate (GFR) (1.93 Ϯ 0.08 vs. 2.27 Ϯ 0.10 ml ⅐ min Ϫ1 ⅐ kg body wt Ϫ1 ) and the ability to excrete an acute Na ϩ load (37.1 Ϯ 4.4 vs. 53.7 Ϯ 9.7%) were reduced. (P Ͻ 0.03 and P ϭ 0.03, respectively). In contrast, prenatal betamethasone exposure had no effect on basal GFR, Na ϩ excretion, or the percentage of the Na ϩ load excreted during the experiment in females. Systemic infusions of ANG-(1-7) at 9 ng⅐ min Ϫ1 ⅐ kg Ϫ1 for 2 h had minimal effects on basal GFR, renal plasma flow, and Na ϩ excretion in males but increased Na ϩ excretion in females. However, the percentage of Na ϩ load excreted during ANG-(1-7) infusion did not change in prenatal betamethasone-exposed females (113.1 Ϯ 14.2 vs. 98.1 Ϯ 12.2%) compared with the significant increase in vehicle females (139.2 Ϯ 22.3 vs. 92.2 Ϯ 7.5%) (P ϭ 0.01). The data indicate that antenatal betamethasone exposure produces gender-specific alternations in renal function and thus suggest that different mechanisms underlie the antenatal steroid-induced elevations in blood pressure in male and female offspring. prenatal steroid exposure; sodium load; glomerular filtration rate; sodium excretion; angiotensin-(1-7) SINCE ANTENATAL STEROID TREATMENT became the standard of care for enhancing fetal lung maturation in pregnancies threatened by premature labor between 24 and 34 wk of gestation, the use of corticosteroid therapy in the United States has increased from Ͻ15% of eligible pregnancies in 1990 to Ͼ75% in 1995 (1, 3). However, clinical epidemiological studies show an association between antenatal glucocorticoid administration and altered vascular function (7,46), suggesting that exposure to excess glucocorticoids in the prenatal period may have untoward consequences in adult offspring.We and others have shown using sheep and rat experimental models that prenatal steroid exposure results in elevated blood pressure in adulthood (8,10,14,36). Although there are likely multiple targets influencing the effect of steroids on blood pressure, several recent studies have suggested that altered kidney development induced by antenatal glucocorticoids may contribute to the elevations in arterial blood pressure (35,36,53). It is well known that the kidneys play a major role in the long-term regulation of arterial pressure and that change in renal function may lead to alterations in Na ϩ and water balance and blood pressure (19). In a rat model, Ortiz et al. (35,36) observed that prenatal exposure to dexamethasone on days 15 and 16 of gestation induced 30 and 20% reductions in glomerular number in offspring compared with controls when assessed at 60 -70 days and 6 -9 mo of age, ...

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“…Moreover, this model is particularly applicable to IUGR in the developed world, where IUGR occurs in adequately nourished mothers. Although impaired nephrogenesis and glomerular filtration rate (GFR) have been observed in domestic IUGR piglets, it is unknown whether these structural outcomes are associated with the later development of hypertension [5,10] . Moreover, postnatal factors, including diet and accelerated catch-up growth following low birth weight, are also important for the manifestation of adult hypertension in low birth weight offspring [11,12] .…”

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“…Copyright © 2011 S. Karger AG, Basel Studies investigating the long-term impact of fetal adaptation to a poor intrauterine environment have demonstrated an inverse relationship between fetal growth and blood pressure (BP) in adulthood in induced [1][2][3] and naturally occurring [3, 4] models of intrauterine growth restriction (IUGR). About 80-90% of the human incidence of IUGR is thought to be due to impaired nutrient perfusion through the placenta, leading to reduced birth weight in the offspring in addition to altered organ development, including reduced nephron number and impaired renal function [5,6] . The naturally occurring spontaneous IUGR piglet (i.e., runt) represents a suitable model for IUGR in newborn infants [7,8] …”

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confidence: 99%

Low Birth Weight Is Associated with Reduced Nephron Number and Increased Blood Pressure in Adulthood in a Novel Spontaneous Intrauterine Growth-Restricted Model in Yucatan Miniature Swine

Myrie¹,

McKnight²,

Vliet

et al. 2011

Neonatology

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Background: Impaired fetal growth and rapid postnatal growth are associated with programming of hypertension and metabolic syndrome in adulthood. Objectives: This study evaluated this phenomenon in a novel spontaneous intrauterine growth-restricted (IUGR) model in Yucatan miniature pigs. Methods: IUGR piglets (n = 6, 3 days old, 0.73 ± 0.11 kg) were paired with a normal weight (NW) same-sex littermate (n = 6, 1.11 ± 0.13 kg), fed milk replacer for 4 weeks followed by a standard diet ad libitum for 5 h/day. At 9 months of age, arterial blood pressure (BP) telemeters were implanted to assess BP before (0.5% NaCl) and after (4.5% NaCl) a 7-day salt-loading period. At 10 months of age, nephron numbers were determined. Results: Prior to sexual maturity, IUGR pigs showed greater (p < 0.05) relative feed intake and experienced significant catch-up growth. Adult IUGR pigs also had higher BP (diastolic BP: 93.8 ± 5.5 vs. 90.0 ± 8.7 mm Hg, p < 0.05) and 43% fewer nephrons per kidney (p < 0.05). Nephron number was positively associated with birth weight and negatively correlated with BP (p < 0.05). Acute salt loading increased BP in both groups (p < 0.05); however, the degree of salt sensitivity was similar between groups (p > 0.05). Conclusions: In conclusion, IUGR piglets have reduced nephron endowment associated with a modest BP increase in early adulthood. This new model can be used to conduct longitudinal mechanistic studies on the early programming phenomenon.

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Developmental origins of adult hypertension: new insights into the role of the kidney

Cited by 31 publications

References 33 publications

Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues

Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

Low Birth Weight Is Associated with Reduced Nephron Number and Increased Blood Pressure in Adulthood in a Novel Spontaneous Intrauterine Growth-Restricted Model in Yucatan Miniature Swine

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