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

Abstract

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.

Fetal Kidney Programming by Maternal Smoking Exposure: Effects on Kidney Structure, Blood Pressure and Urinary Sodium Excretion in Adult Offspring

“…In the current study, the putative tubular functional changes and absolute reduction of glomeruli number could be associated with glomerular hyperfiltration/overflow that may account for the glomerular filtration barrier breakdown and early glomerulosclerosis [4,5,6,10] in this smoking model. Although the data presented here do not offer any support for the kidney hemodynamic factors or humoral hypothesis, we cannot rule out the possibility that several humoral factors or renal vascular resistance and blood flow changes, induced by maternal tobacco exposure, may be involved in mediating the urinary sodium response.…”

“…Although the present study shows a reduced glomeruli number (about 13%) in Sk, this finding as well as the glomerular volume was not different when compared to the control group data. In previous studies, we and others have demonstrated in different models of fetal programming, that even when associated with decreased glomeruli number units, the offspring maintain a normal whole-kidney glomerular filtration rate, estimated by creatinine clearance, suggesting, in fact, a compensatory glomerular hyperfiltration [4,5,6,10]. …”

“…Low birth weight (LBW) is also associated with impaired renal growth, raised blood pressure and impaired renal function [8,9,10,11]. A reduction in nephron number and, therefore, in the whole-kidney glomerular filtration area would result in reduced sodium excretory capacity, enhanced susceptibility to hypertension and reduced renal reserve; therefore, the limiting compensation for renal injury may, at least in part, explain the higher prevalence of hypertension and renal disease observed in populations with a high prevalence of low birth weight [4,5,6,10]. …”

“…These adaptations may be beneficial in the short term, but may have adverse consequences in postnatal life [1]. Fetal programming by different insults results in low birth weight and reduction in nephron number [2,3,4,5,6,7], and increases the risk for adult development of cardiovascular and renal diseases [4,5,6]. Low birth weight (LBW) is also associated with impaired renal growth, raised blood pressure and impaired renal function [8,9,10,11].…”

A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

“…Moreover, the RAAS and nephron quantity in offspring were altered upon different insults during IU/L. Undernutrition during IU/L leads to reduced nephron numbers in the kidney in offspring [54]. Protein restriction during IU/L in a rat model induced increased gene expression of the renal AT 1 a- and AT 2 - receptor, but not of the renal AT 1 b-receptor, in offspring at postnatal day 28 [55].…”