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Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways

BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade i...

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Autores principales: Luzardo, Ricardo, Silva, Paulo A., Einicker-Lamas, Marcelo, Ortiz-Costa, Susana, Tavares do Carmo, Maria da Graça, Vieira-Filho, Leucio D., Paixão, Ana D. O., Lara, Lucienne S., Vieyra, Adalberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128598/
https://www.ncbi.nlm.nih.gov/pubmed/21747933
http://dx.doi.org/10.1371/journal.pone.0021232
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author Luzardo, Ricardo
Silva, Paulo A.
Einicker-Lamas, Marcelo
Ortiz-Costa, Susana
Tavares do Carmo, Maria da Graça
Vieira-Filho, Leucio D.
Paixão, Ana D. O.
Lara, Lucienne S.
Vieyra, Adalberto
author_facet Luzardo, Ricardo
Silva, Paulo A.
Einicker-Lamas, Marcelo
Ortiz-Costa, Susana
Tavares do Carmo, Maria da Graça
Vieira-Filho, Leucio D.
Paixão, Ana D. O.
Lara, Lucienne S.
Vieyra, Adalberto
author_sort Luzardo, Ricardo
collection PubMed
description BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood.
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spelling pubmed-31285982011-07-11 Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways Luzardo, Ricardo Silva, Paulo A. Einicker-Lamas, Marcelo Ortiz-Costa, Susana Tavares do Carmo, Maria da Graça Vieira-Filho, Leucio D. Paixão, Ana D. O. Lara, Lucienne S. Vieyra, Adalberto PLoS One Research Article BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood. Public Library of Science 2011-07-01 /pmc/articles/PMC3128598/ /pubmed/21747933 http://dx.doi.org/10.1371/journal.pone.0021232 Text en Luzardo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Luzardo, Ricardo
Silva, Paulo A.
Einicker-Lamas, Marcelo
Ortiz-Costa, Susana
Tavares do Carmo, Maria da Graça
Vieira-Filho, Leucio D.
Paixão, Ana D. O.
Lara, Lucienne S.
Vieyra, Adalberto
Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title_full Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title_fullStr Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title_full_unstemmed Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title_short Metabolic Programming during Lactation Stimulates Renal Na(+) Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways
title_sort metabolic programming during lactation stimulates renal na(+) transport in the adult offspring due to an early impact on local angiotensin ii pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128598/
https://www.ncbi.nlm.nih.gov/pubmed/21747933
http://dx.doi.org/10.1371/journal.pone.0021232
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