title: Metabolic programming during lactation stimulates renal Na+ transport in the adult offspring due to an early impact on local angiotensin II pathways.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Ricardo
authors: R
authors: Luzardo
authors: Paulo A
authors: PA
authors: Silva
authors: Marcelo
authors: M
authors: Einicker-Lamas
authors: Susana
authors: S
authors: Ortiz-Costa
authors: Maria da Graça Tavares
authors: Mda G
authors: do Carmo
authors: Leucio D
authors: LD
authors: Vieira-Filho
authors: Ana D O
authors: AD
authors: Paixão
authors: Lucienne S
authors: LS
authors: Lara
authors: Adalberto
authors: A
authors: Vieyra
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004435:Eating / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007774:Lactation / Q000378:metabolism*; D008297:Male; D044342:Malnutrition / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009035:Mothers; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D014886:Weaning
chemical_list: D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003094:Collagen; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase