Placental malnutrition changes the regulatory network of renal Na-ATPase in adult rat progeny: Reprogramming by maternal α-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 (AT1R and AT2R) to kidney Na+-ATPase in adulthood, and how maternal treatment with α-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 α-tocopherol during lactation. Malnutrition during pregnancy increased maternal hepatic and adult offspring renal malondialdehyde levels, which returned to control after supplementation with α-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 AT1R and AT2R, decrease in membrane PKC activity, selective decrease of the PKCε isoform expression, and increase in PKA activity with no change in PKA α-catalytic subunit expression. These alterations were reprogrammed to normal levels by α-tocopherol during lactation. The influence of α-tocopherol on the signaling machinery in adult offspring indicates selective non-antioxidant effects at the gene transcription and protein synthesis levels.

Research highlights
► Prenatal malnutrition programs alterations in Na transport in the adult offspring.
► Alterations in Na transport are associated with ouabain-insensitive Na-ATPase.
► Programming alters angiotensin II receptors expression.
► Physiological response of Na pump to angiotensin II is lost.
► Programming decreases PKC and increases PKA.
► Maternal α-tocopherol during lactation restores physiological control of Na pump.