Fetal kidney programming by severe food restriction: Effects on structure, hormonal receptor expression and urinary sodium excretion in rats

Mar 14, 2013Journal of the renin-angiotensin-aldosterone system : JRAAS

How Severe Food Restriction During Pregnancy Affects Fetal Kidney Development, Hormone Receptors, and Sodium Excretion in Rats

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Abstract

Offspring with severe food restriction in utero show a 35% reduction in nephron numbers.

Blood pressure is increased in 12-week-old offspring subjected to food restriction.
Expression of angiotensin II receptors significantly decreases with food restriction.
Glucocorticoid and mineralocorticoid receptor expression increases in food-restricted offspring.
Decreased urinary sodium excretion is observed in the food-restricted group.
Changes in renal function may contribute to increased sodium retention and hypertension in adulthood.

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INTRODUCTION: The present study investigates, in 23-day-old and adult male rats, the effect of severe food restriction in utero on blood pressure (BP), and its association with nephron structure and function changes, angiotensin II (AT1R/AT2R), glucocorticoid (GR) and mineralocorticoid (MR) receptor expression.

MATERIALS AND METHODS: The daily food supply to pregnant rats was measured and one group (n=15) received normal quantity of food (NF) while the other received 50% of that (FR50%) (n=15). Kidneys were processed to AT1R, AT2R, MR, and GR immunolocalization and for western blotting analysis. The renal function was estimated by creatinine and lithium clearances in 12-week-old offspring.

RESULTS: By stereological analyses, FR50% offspring present a reduction of nephron numbers (35%) with unchanged renal volume. Expression of AT1R and AT2R was significantly decreased in FR50% while the expression of GR and MR increased in FR50%. We also verified a pronounced decrease in urinary sodium excretion accompanied by increased BP in 12-week-old FR50% offspring.

CONCLUSION: The current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption, and this might potentiate the programming of adult hypertension. It is plausible to arise in the current study an association between decreasing natriuresis, reciprocal changes in renal AngII and steroid receptors with the hypertension development found in FR50% compared with age-matched NF offspring.

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Fetal kidney programming by severe food restriction: Effects on structure, hormonal receptor expression and urinary sodium excretion in rats

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