High Sodium Intake Increases Blood Pressure and Alters Renal Function in Intrauterine Growth–Retarded Rats

Abstract

Abstract-A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria. Key Words: hypertension, sodium-dependent Ⅲ sodium A healthy intrauterine environment is prerequisite for normal development. A suboptimal intrauterine environment may permanently alter some tissues and organs that enable the fetus to survive in utero but cause a predisposition to (cardiovascular) disease later in life. 1 Particularly, the development of the kidney can be affected by this process of fetal programming. 2 A possible mechanism might be an impaired nephrogenesis as a result of a suboptimal intrauterine environment. This may lead to reduced nephron endowment during development, which is associated with high blood pressure 3 and renal dysfunction 4 in the adult. Previous studies in our laboratory have shown that a suboptimal intrauterine environment, induced by bilateral ligation of the uterine arteries of pregnant rats, resulted in a decreased glomerular number, an increased glomerular size, and an altered renal function in the adult offspring. In young adults, we could not demonstrate a change in blood pressure as a result of a suboptimal fetal environment, but we have shown that the renal compensatory capacity after unilateral nephrectomy is reduced. 5 Not only fetal programming, but also dietary influences such as high sodium intake, increase the risk of cardiovascular and renal diseases, independently of other cardiovascular risk factors, including blood pressure. 6 High sodium intake may have de...

Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring

“…A prenatal 5% protein diet also produced offspring that were salt sensitive as adults (45), although others have reported that protein under-nutrition did not produce salt sensitivity (25). Finally, uterine artery ligation during the final week of pregnancy also produced adult offspring that increased blood pressure significantly when given 2% NaCl to drink (34). In the present investigation we used a HS challenge to test the hypothesis that a prenatal HS diet could also program salt sensitivity.…”

“…Sprague-Dawley rats are not genetically salt sensitive, that is, a HS diet produces only a modest increase in blood pressure (15,28). However, there is some indication that perinatal HS and other models of fetal programming may impart a significant permanent salt sensitivity (8,34,45). The final hypothesis addressed was that a maternal HS diet limited to the period of pregnancy would produce offspring that were salt sensitive as adults.…”

Chronic Kidney Disease: A Life Course Health Development Perspective

“…In addition, increased glomerular apoptosis has been observed (Pham et al 2003). Studies of the mechanism by which intrauterine growth retardation may induce hypertension have suggested a role for the renin-angiotensin system, renal sympathetic activation, maternal glucocorticoid and fetal kidney 11beta-hydroxysteroid dehydrogenase type 2 activation, and increased sodium retention (Baserga et al 2010;Ojeda et al 2007;Grigore et al 2007;Langley-Evans 1997;Sanders et al 2005;Franco et al 2012). Several studies have indicated that altered gene expression may be the result of epigenetic regulation (Baserga et al 2010;Pham et al 2003;Woroniecki et al 2011).…”

Molecular interactions between the Wilms' tumor transcription factor and the aryl hydrocarbon receptor during nephrogenesis and its impact on fetal programming of renal disease.

“…LBW adults with low nephron number are prone to nnicroalbuminuria, proteinuria, and decreased glomerular filtration (Celsi et al, 1998;Nwagwu et al, 2000;Sanders et al, 2005). Thus, it is likely that intrauterine factors, including PAHs, compromise renal development resulting in low nephron number.…”

“…Proposed mechanism IOf fetall programming in hypertension, renal disease, and glomerulalr filtration. Intrauterine factors, including PAHs, compromise renal development resulting in low nephron number (Celsi et a/., 1998;Nwagwu et al, 2000;Sanders et al, 2005 . Using a metanephric kidney organ culture system, we have shown that exposure to BaP, a hydrocarbon ligand for the AHR, inhibits nephrogenesis and increases -KTS/+KTS WT1 mRNA ratios.…”