Effects of placental insufficiency on the ovine fetal renin-angiotensin system

Zhang, David Y.; Lumbers, Eugenie R.; Simonetta, Giuseppe; Wu, June J.; Owens, Julie A.; McMillen, I. Caroline

doi:10.1017/s0958067000019394

Cited by 22 publications

(20 citation statements)

References 10 publications

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“…There was no significant change in the expression of renin mRNA in the kidney in response to placental restriction. This contrasts with the previous findings of Zhang et al (41), who reported that renin mRNA was reduced in the kidney of placentally restricted fetal sheep. Consistent with the results of Zhang et al, it has been demonstrated that, in the rat, restriction of maternal protein intake during pregnancy suppressed renin mRNA levels in the kidneys of offspring (42).…”

contrasting

confidence: 99%

Placental Restriction Increases the Expression of Prostaglandin Endoperoxide G/H Synthase-2 and EP2 mRNA in the Fetal Sheep Kidney during Late Gestation

WILLIAMS

2002

Pediatric Research

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contrasting

confidence: 99%

Placental Restriction Increases the Expression of Prostaglandin Endoperoxide G/H Synthase-2 and EP2 mRNA in the Fetal Sheep Kidney during Late Gestation

WILLIAMS

2002

Pediatric Research

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“…We found suppression of renal renin mRNA and renin concentrations as well as renin immunostaining, and reduced tissue ANGII levels during this critical developmental window, thus supporting our overarching hypothesis. Further support is provided by the recent finding that the intrarenal RAS is also suppressed in fetal sheep with placental insufficiency, another model of intrauterine malnutrition (32).…”

Section: Discussionmentioning

confidence: 83%

Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

et al. 2001

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Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn reninangiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p Ͻ 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 Ϯ 0.002 ng/mg, LP versus 0.146 Ϯ 0.016 ng/mg, NP, p Ͻ 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 Ϯ 1 mm Hg, LP versus 126 Ϯ 1 mm Hg, NP, p Ͻ 0.00007), and GFR normalized to kidney weight was reduced in LP (p Ͻ 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 Ϯ 1,694, LP versus 28,917 Ϯ 2,342, NP, p Ͻ 0.03), and individual glomerular volume was higher (1.81 Ϯ 0.16 10 6 m 3 , LP versus 1.11 Ϯ 0.10 10 6 m 3 , NP, p Ͻ 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult. Abbreviations RAS, renin-angiotensin system ERPF, effective renal plasma flow NP, normal protein (19%) diet LP, low-protein (8.5%) diet ANGII, angiotensin II PAH, para-amino hippurate A decade ago, Barker et al. first reported an inverse relationship between birth weight and death from cardiovascular disease in adulthood (1). Subsequently, a number of epidemiologic studies in different parts of the world have found a relationship between early growth patterns and the risk of cardiovascular disease in adulthood (2-8). Although these findings remain somewhat controversial (9), the majority of evidence indicates that even within the "normal" range of birth weights, babies that are born smaller have a higher risk of death from cardiovascular disease when they reach adulthood. This indicates that some factor or factors in the perinatal environment, probably related at least in part to maternal nutrition, can "program" the individual for increased cardiovascular risk later in life. However, the precise physiologic and molecular mechanisms by which this programming occurs are unknown.Recently, a rat model of perinatal protein restriction has been identified that has several features in common with the observations in humans, suggesting that this may be a good animal model of the human condition. In particular, offspring ABSTRACT460

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“…Different animal models include dietary undernutrition induced by global food restriction (9,10) or protein restriction during gestation (11,12,13,14,15), maternal hypoxia during gestation (16,17), placental insufficiency (18,19,20,21,22), or prenatal glucocorticoid treatment (23,24).…”

Section: Sex Differences In Fetal Programming: Animal Studiesmentioning

confidence: 99%