Placental oxidative stress in malnourished rats and changes in kidney proximal tubule sodium ATPases in offspring

P>Intrauterine malnutrition has been linked to the development of adult cardiovascular and renal diseases, which are related to altered Na+ balance. Here we investigated whether maternal malnutrition increases placental oxidative stress with subsequent impact on renal ATP-dependent Na+ transporters in the offspring. Maternal malnutrition was induced in rats during pregnancy by using a basic regional diet available in north-eastern Brazil. Placental oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances, which were 35-40% higher in malnourished dams (MalN). Na+ pumps were evaluated in control and prenatally malnourished rats (at 25 and 90 days of age). Identical Na+/K+-ATPase activity was found in both groups at 25 days (approximately 150 nmol P-i/mg per min). However, although Na+/K+-ATPase increased by 40% with growth in control rats, it remained constant in pups from MalN. In juvenile rats, the activity of the ouabain-insensitive Na+-ATPase was higher in MalN than in controls (70 vs 25 nmol P-i/mg per min). Nevertheless, activity did not increase with kidney and body growth: at 90 days, it was 50% lower in MalN than in controls. The maximal stimulation of the Na+-ATPase by angiotensin (Ang) II was 35% lower in MalN than in control rats and was attained only with a much higher concentration of the peptide (10-10 mol/L) than in controls (10-14 mol/L). Protein kinase C activity, which mediates the effects of AngII on Na+-ATPase was only one-third of normal values in the MalN group. These results indicate that placental oxidative stress may contribute to fetal undernutrition, which leads to later disturbances in Na+ pumps from proximal tubule cells.