Abstract
Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1(R)) or type 2 (AT2(R)) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1(R) is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2(R) expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na(+)/K(+)-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na(+)/K(+)-ATPase, leading to increased Na(+) reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death.
Highlights
The role of the kidney in the pathogenesis of hypertension has long been established, recent studies challenge renal hegemony and suggest an important role for vascular cells as well [1,2]
The purpose of the present review is to describe some of the mechanisms that can affect the kidney, with special focus on the renin-angiotensin system (RAS)
We have concentrated on one organ, the kidney, and shown that adult hypertension, programmed by maternal exposure to a low-protein diet, is linked to marked changes in the renal expression of the glucocorticoid receptor, 11ß-HSD2, and components of the RAS
Summary
The role of the kidney in the pathogenesis of hypertension has long been established, recent studies challenge renal hegemony and suggest an important role for vascular cells as well [1,2] In recent years, this view has expanded and includes the concept that chronic hypertension and kidney dysfunction are related to events that occur during the prenatal period. This view has expanded and includes the concept that chronic hypertension and kidney dysfunction are related to events that occur during the prenatal period This relationship between fetal programming of disease and the kidney suggests that several mechanisms can predispose to hypertension during adulthood through impaired nephrogenesis. Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment [7]
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