How the Kidney Is Impacted by the Perinatal Maternal Environment to Develop Hypertension1

Abstract

Environmental conditions during perinatal development such as maternal undernutrition, maternal glucocorticoids, placental insufficiency, and maternal sodium overload can program changes in renal Na(+) excretion leading to hypertension. Experimental studies indicate that fetal exposure to an adverse maternal environment may reduce glomerular filtration rate by decreasing the surface area of the glomerular capillaries. Moreover, fetal responses to environmental insults during early life that contribute to the development of hypertension may include increased expression of tubular apical or basolateral membrane Na(+) transporters and increased production of renal superoxide leading to enhanced Na(+) reabsorption. This review will address the role of these potential renal mechanisms in the fetal programming of hypertension in experimental models induced by maternal undernutrition, fetal exposure to glucocorticoids, placental insufficiency, and maternal sodium overload in the rat.

Maternal fructose-intake-induced renal programming in adult male offspring

“…Oxidative stress has been reported to play a role in renal programming of the offspring [2][3][4]. We also reported that ADMAinduced NO/reactive oxygen species (ROS) imbalance is involved in the development of hypertension in several programming models [6][7][8][9][10].…”

“…Early-life environmental insults during critical periods of kidney development can elicit epigenetic alterations, morphological changes and functional adaptations, leading to metabolic syndrome and related disorders in adult life [2][3][4]. Despite the rising incidence of maternal obesity, little attention has been paid to maternal fructose-intake-induced permanent changes in renal structure and function in the offspring, referred to as renal programming [5].…”

“…The kidney can be programmed by a variety of pre-, peri-and postnatal factors [2][3][4]. We recently observed that renal programming and hypertension developed in the adult male offspring of mother rats exposed to caloric restriction [6,7], diabetes [8], dexamethasone treatment [9,10] and high-fructose (HF) diet [11].…”

“…We recently observed that renal programming and hypertension developed in the adult male offspring of mother rats exposed to caloric restriction [6,7], diabetes [8], dexamethasone treatment [9,10] and high-fructose (HF) diet [11]. A number of mechanisms, including glucocorticoid effects, oxidative stress, epigenetic regulation, alterations of renin-angiotensin system (RAS), impaired tubular sodium handling and reduction in nephron numbers, have been put forward to interpret renal programming [2][3][4]. However, currently available knowledge gathered from different programming models is unable to identify the common underlying mechanism that drives the programming processes.…”

Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status

“…In fact, oxidative stress has been implicated in fetal programming [7] and several studies in animal models of IUGR have evidenced that oxidative damage is present in key organs for cardiovascular control such as the heart [8] the kidney [9] [10] and blood vessels [11]. However, the presence of oxidative damage in animals with already established pathology does not determine whether oxidative stress is the cause or consequence of the cellular alterations [12].…”