Long-Term Modification of the Excretion of Prostaglandin E&lt;sub&gt;2&lt;/sub&gt; by Fetal Exposure to a Maternal Low Protein Diet in the Rat

Sherman, Rachel C.; Jackson, Alan A.; Langley‐Evans, Simon C.

doi:10.1159/000012773

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…Similar adaptations were found for PGDH at 28 days and in the adult that was accompanied by a lower PGE 2 content in the adult kidney. Taken together, these findings suggest enhanced degradation of PGs in the kidney as seen in offspring born to dams fed a low-protein diet (24).…”

Section: Discussionmentioning

confidence: 69%

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Brennan

Kaufman²,

Reynolds³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism, and receptor expression. Since the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control-fed mothers and eight nutrient-restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient-restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE2, with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development and decreased blood pressure.kidney; nutrient restriction; offspring; prostaglandins MATERNAL NUTRIENT RESTRICTION during pregnancy has been previously shown to affect the renal development of the offspring. In the sheep, nutrient restriction targeted to the period of early kidney development subsequently increases organ size as well as affecting kidney shape and promotes glucocorticoid receptor (GCR) mRNA abundance (32). Global nutrient restriction (9) and protein restriction in particular can both reduce the total number of nephrons formed in developing rat kidneys, but this does not necessarily result in raised blood pressure in the offspring (11). The mechanisms by which maternal nutritional manipulation acts to compromise fetal development and ultimately adult health remain uncertain. It has been proposed that this is dependent in part on increased maternal corticosterone concentrations acting directly on the fetus (16). This proposal is supported by the finding that maternal administration of dexamethasone, which crosses the placenta to the fetus during pregnancy, can cause similar cardiovascular outcomes as observed with maternal food deprivation (40); indeed, dexamethasone administration also results in reduced maternal food consumption, suggesting a behavioural effect on appetite (37, 40). Recently, it has been shown that a transient increase in maternal corticosterone on days 14 and 15 of pregnancy in rats can impair development of the intra-...

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Section: Discussionmentioning

confidence: 69%

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Brennan

Kaufman²,

Reynolds³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…As NO increases MBF and thus sodium excretion, a reduction in NO bioavailability could lead to sodium retention. Conversely, PGE 2 , which increases MBF, is increased in the LP rat [36]. Renal oxidative stress is increased in LP rats, and treatment with the superoxide dismutase mimetic Tempol [35] or the lipid peroxidation inhibitor lazaroid [37] lowers blood pressure.…”

Section: Discussionmentioning

confidence: 95%

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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“…Na + reabsorption by the TAL (thick ascending limb) is also regulated by PGE 2 (prostaglandin E 2 ) which has been reported to inhibit NKCC2 activity in cultured mouse TAL cells [42]. Urinary PGE 2 excretion is increased in 4-week-old LP rats [43], which raises the possibility that net NKCC2 transport is inhibited, despite increased transporter expression.…”

Section: Discussionmentioning

confidence: 99%

Prenatal programming of renal sodium handling in the rat

Alwasel

Ashton

2009

Clinical Science

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Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl- co-transporter (NKCC2) and the Na+/Cl- co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na+ excretion rates (1.6+/-0.3 and 3.0+/-0.4 mumol.min-1.100 g-1 of body weight in control male and LP male respectively; P<0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5+/-0.2 and 3.0+/-0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase alpha1 subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4+/-1.8 and 17.7+/-1.2 nmol of phosphate.mug-1 of protein.h-1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the alpha1 subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure-natriuresis mechanism; however, the loss of the Na+/K+ ATPase alpha1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.

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Long-Term Modification of the Excretion of Prostaglandin E<sub>2</sub> by Fetal Exposure to a Maternal Low Protein Diet in the Rat

Cited by 12 publications

References 26 publications

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

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

Prenatal programming of renal sodium handling in the rat

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