Role of postnatal dietary sodium in prenatally programmed hypertension

Stewart, Tyrus; Ascani, Jeannine; Craver, Randall; Vehaskari, V. Matti

doi:10.1007/s00467-009-1196-8

Cited by 21 publications

(19 citation statements)

References 34 publications

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“…When LP pups were weaned onto a low-(0.03%), standard-(0.3%), or high-(3%) salt diet for 3 weeks, there was a positive correlation between salt intake and blood pressure in LP rats but not controls. Longitudinal blood pressure profiling showed that brief exposure to a low-salt diet had a long-lasting antihypertensive effect, whereas those briefly fed a high-salt diet continued to have increased blood pressure up to 51 weeks of age [30].…”

Section: Discussionmentioning

confidence: 99%

Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat

Alwasel

Ashton

2011

Pediatr Nephrol

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Hypertension and renal dysfunction can be programmed in the rat by prenatal exposure to a low-protein (LP) diet. Expression of the renal thick ascending limb (TAL) sodium transporter NKCC2 is up-regulated, which has been predicted to result in greater sodium reabsorption. However, we have shown that LP rats excrete more not less sodium. The aim of this study was to determine whether the increased abundance of sodium:potassium:chloride (Na(+):K(+):2Cl(-)) co-transporter (NKCC2) leads to enhanced sodium uptake by the TAL. Pregnant Wistar rats were fed a control (18%) or LP (9%) diet. Amiloride (AM), bendroflumethiazide (BF), and furosemide (FUR) were administered acutely to male offspring at 4 weeks of age. Fractional excretion of sodium (FE(Na)) was significantly greater in vehicle-infused LP rats (3.0 ± 0.3%) compared with controls (1.7 ± 0.5, P < 0.01). FE(Na) by the LP proximal tubule did not differ from controls, whereas FE(Na) by the distal tubule was significantly greater (P < 0.01). These differences were abolished by the administration of AM + BF (equivalent to the outflow from the TAL) and AM + BF + FUR (equivalent to the outflow from the proximal tubule), suggesting that the increase in NKCC2 expression was not functional. However, during acute salt loading, the LP rat pressure natriuresis curve was shifted rightward, implying that raised systemic blood pressure is required to match urinary sodium excretion with dietary intake. These data suggest that renal sodium handling is impaired in the LP rat but that this is not due to increased NKCC2 expression.

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Section: Discussionmentioning

confidence: 99%

Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat

Alwasel

Ashton

2011

Pediatr Nephrol

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“…Metabolic and vascular disorders, themselves "perinatally programmed", may additionally affect renal function and renal structure and lead to hypertension and early chronic kidney disease (see text). ESRD end-stage renal disease, IUGR intrauterine growth restriction, GFR glomerular filtration rate, GC glucocorticoids, GS glomerular sclerosis, HTN hypertension, P GC glomerular capillary pressure, SNGFR single nephron glomerular filtration rate glomerular hyperfiltration and induce systemic hypertension and glomerular injuries in adult animals with a reduced nephron number [83,93,94,111,157]. Such a sequence has been shown to result from an up-regulation of the RAS [110,158].…”

Section: Experimental Studiesmentioning

confidence: 96%

“…This provides evidence of abnormal programming of the RAS and glomerular function in offspring of pregnancies in which there is impaired maternal renal function [105]. Aside from reduced nephron endowment, hypertension can be due to an alteration in the tubular handling of sodium with increased sodium reabsorption, over-activity of the sympathetic nerve, and oxidative stress [34,63,[106][107][108][109][110][111]. Increased expression of the renal tubular Na+:K+:2Cl-co-transporter (NKCC2) and loss of the Na+:K + ATPase alpha1 subunit from the inner medulla have been demonstrated in MLP rat offspring, suggesting that altered renal sodium handling is also programmed prenatally [112].…”

Section: Altered Nephrogenesis and Increased Arterial Blood Pressure mentioning

confidence: 97%

“…The kidneys of 13 month-old male IUGR offspring with a rapid catch-up are characterized by enhanced telomere shortening, and hence cell senescence [142]. Interestingly, telomere shortening is unchanged in IUGR offspring with slow postnatal growth, which may suggest that the glomerular adaptive mechanism is slight enough to induce glomerular damage in such a situation: slow postnatal growth or reduced salt intake in IUGR offspring prevents the development of hypertension and of renal injury [48, 98,111]. Enhanced SNGFR and P GC resulting from miss-match between overfeeding and reduced renal filtration capacities, is associated with structural glomerular changes, including enlargement of glomerular capillaries and podocyte injuries [92,159].…”

Section: Experimental Studiesmentioning

confidence: 99%

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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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“…Rodents, in which nephrogenesis is completed during the first 2 weeks after birth, can be programmed during this period to develop hypertension in adult life by maneuvers such as protein restriction 1 and dietary salt overload. 2 The mechanisms responsible for blood pressure heightening in this setting are presently obscure, and may involve subtle changes in renal handling of sodium. 3 Treatment with suppressors of the renin-angiotensin system (RAS) during rat lactation (first 3 weeks after birth) has also been shown to promote hypertension later in life.…”

Section: Introductionmentioning

confidence: 99%

Programmed hypertension in rats treated with a NF-κB inhibitor during nephrogenesis: renal mechanisms

et al. 2011

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Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-jB system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg -1 day -1 orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-jB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters.

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Role of postnatal dietary sodium in prenatally programmed hypertension

Cited by 21 publications

References 34 publications

Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat

Segmental sodium reabsorption by the renal tubule in prenatally programmed hypertension in the rat

Adverse consequences of accelerated neonatal growth: cardiovascular and renal issues

Programmed hypertension in rats treated with a NF-κB inhibitor during nephrogenesis: renal mechanisms

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