Development of fetal brain renin–angiotensin system and hypertension programmed in fetal origins

Mao, Caiping; Shi, Lijun; Xu, Fulin; Zhang, Li; Xu, Zhice

doi:10.1016/j.pneurobio.2008.12.001

Cited by 32 publications

(30 citation statements)

References 132 publications

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“…Both AT 1 R and AT 2 R have been suggested to be involved in cellular development, including cellular proliferation and differentiation [8,9,10,11,12,36]. In light of this, at least one explanation was considered for the data gained in the present study: an increase of fetal renal AT 1 R and a decrease of AT 2 R following hypoxia may contribute to cell growth, differentiation, migration and apoptosis [37,38] in the cortical zone of the fetal kidney and may be involved in alterations in glomerular and tubular histology. Although future studies are needed for further clarification, the present study was the first to demonstrate that the fetal renal AT 1 R/AT 2 R ratio was significantly increased following hypoxia in association with glomerular and tubular alterations in utero.…”

Section: Discussionmentioning

confidence: 80%

Changes of Renal AT1/AT2 Receptors and Structures in Ovine Fetuses following Exposure to Long-Term Hypoxia

Mao

Hou

et al. 2009

Am J Nephrol

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Background/Aims: The present study tested the hypothesis that chronic hypoxia adversely affects renal development in the ovine fetus. Methods: Kidneys were collected from near-term fetuses of pregnant ewes maintained at sea level or high altitude (3,801 m, PaO₂: approx. 60 mm Hg) for 110 days (n = 6 for each group). Results: Long-term high altitude hypoxia reduced the fetal kidney/body weight ratio. Histological analysis showed a significant enlargement in the Bowman’s space and swelling of tubule epithelial cells in the kidney of the hypoxic fetus. The histological alterations were limited to the cortical, but not medullary, zone. These alterations were associated with an increase in serum creatinine and a decrease in the BUN-to-creatinine ratio in hypoxic fetuses. Angiotensin II receptors (AT₁R and AT₂R) were detected in the glomerular and tubular regions of the kidney. Chronic hypoxia caused a significant increase in AT₁R and a decrease in AT₂R protein and mRNA abundance, resulting in a large increase in the AT₁R/AT₂R ratio in the fetal kidney. Conclusion: The results demonstrate an adverse effect of chronic hypoxia on renal AT₁R and AT₂R expression and functions in the fetus, suggesting a possible role of fetal hypoxia in the programming of renal diseases in fetal origins.

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Section: Discussionmentioning

confidence: 80%

Changes of Renal AT1/AT2 Receptors and Structures in Ovine Fetuses following Exposure to Long-Term Hypoxia

Mao

Hou

et al. 2009

Am J Nephrol

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“…Cardiovascular functions of the RAS system are conserved in teleosts, and agt was similarly increased along with acute phase response genes in 24 hpf zebrafish exposed to mercury (Le Mevel et al , 2008; Ung et al , 2010). Though not yet explored in zebrafish embryos, the RAS system has been identified as important for fetal cardiovascular response, body fluid balance, and neuroendocrine regulation, and may be involved in fetal programming of hypertension later in life (Mao et al , 2009). …”

Section: Resultsmentioning

confidence: 99%

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

Goodale

Tilton

Corvi

et al. 2013

Toxicology and Applied Pharmacology

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and-independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures.

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“…However, AT 1 :AT 2 mRNA and protein expression ratio in the offspring kidney was significantly increased. An absolute or relative increase of AT 1 may contribute to cell growth and apoptosis (Fitzsimons 1998, Mao et al 2009) in the kidney. The present study demonstrated that renal AT 1 /AT 2 could be significantly altered in the kidney by prenatal HSDs.…”

Section: Discussionmentioning

confidence: 99%

High-salt diets during pregnancy affected fetal and offspring renal renin–angiotensin system

Mao

Liu²,

Bo³

et al. 2013

Journal of Endocrinology

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Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin–angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

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Development of fetal brain renin–angiotensin system and hypertension programmed in fetal origins

Cited by 32 publications

References 132 publications

Changes of Renal AT<sub>1</sub>/AT<sub>2</sub> Receptors and Structures in Ovine Fetuses following Exposure to Long-Term Hypoxia

Changes of Renal AT<sub>1</sub>/AT<sub>2</sub> Receptors and Structures in Ovine Fetuses following Exposure to Long-Term Hypoxia

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

High-salt diets during pregnancy affected fetal and offspring renal renin–angiotensin system

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