Placental malnutrition changes the regulatory network of renal Na-ATPase in adult rat progeny: Reprogramming by maternal alpha-tocopherol during lactation

Prenatal malnutrition is responsible for the onset of alterations in renal Na+ transport in the adult offspring. Here we investigated the molecular mechanisms by which increased formation of reactive oxygen species during prenatal malnutrition affects the pathways that couple angiotensin II (Ang II) receptors (AT(1)R and AT(2)R) to kidney Na+-ATPase in adulthood, and how maternal treatment with alpha-tocopherol can prevent alterations in the main regulatory cascade of the pump. The experiments were carried out on the adult progeny of control and malnourished dams during pregnancy that did or did not receive alpha-tocopherol during lactation. Malnutrition during pregnancy increased maternal hepatic and adult offspring renal malondialdehyde levels, which returned to control after supplementation with alpha-tocopherol. In the adult offspring, placental malnutrition programmed: decrease in Na+-ATPase activity, loss of the physiological stimulation of this pump by Ang II, up-regulation of AT(1)R and AT2R, decrease in membrane PKC activity, selective decrease of the PKC epsilon isoform expression, and increase in PKA activity with no change in PKA alpha-catalytic subunit expression. These alterations were reprogrammed to normal levels by alpha-tocopherol during lactation. The influence of alpha-tocopherol on the signaling machinery in adult offspring indicates selective non-antioxidant effects at the gene transcription and protein synthesis levels. (C) 2010 Elsevier Inc. All rights reserved.