Ouabain Protects Nephrogenesis in Rats Experiencing Intrauterine Growth Restriction and Partially Restores Renal Function in Adulthood.

Intrauterine growth restriction (IUGR) is, in general, accompanied by a reduction of the nephron number, which increases the risk of hypertension and renal dysfunction. Studies have revealed that ouabain can partially restore the number of nephrons during IUGR. However, there is limited information regarding the melioration of nephric structure and function. We used maternal malnutrition to induce an IUGR model in rats. Subsequently, we used a mini-pump to administer ouabain to IUGR rats during pregnancy. Male offspring were divided randomly into two groups. One group was fed a normal diet, whereas the other was fed an isocaloric 8% high-salt diet. Maternal malnutrition led to a reduction in the birth weight and number of nephrons in offspring. At the end of a 40-week follow-up period, offspring from the IUGR group had high blood pressure and abnormal excretion of urinary protein; these parameters were exacerbated in offspring fed a high-salt diet. However, ouabain administration during pregnancy could partially restore the number of nephrons in IUGR offspring, normalize blood pressure, and reduce urinary protein excretion, even when challenged with a high-salt diet. Pathology findings revealed that IUGR, particularly following feeding of a high-salt diet, damaged the ultrastructure of glomeruli, but these harmful effects were ameliorated in offspring treated with ouabain. Collectively, our data suggest that ouabain could rescue nephrogenesis in IUGR newborns and protect (at least in part) the structure and function of the kidney during adulthood even when encountering unfavorable environmental challenges in subsequent life.