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 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 AT1 and decreased the expression of AT2 receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the a (24%) and e (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT2 receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na+ excretion (80%) and intense proteinuri