EXPOSURE TO MATERNAL DIABETES INDUCES SALT-SENSITIVE HYPERTENSION AND IMPAIRS RENAL FUNCTION IN ADULT RAT OFFSPRING

Abstract

Objective: Epidemiological and experimental studies have led to the hypothesis of fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that in utero exposure to maternal diabetes impairs renal development leading to a reduction in nephron number. Little is known on the long term consequences of in utero exposure to maternal diabetes. The aim of the study was to assess, in the rat, long-term effects of in utero exposure to maternal diabetes on blood pressure and renal function in adulthood.

Research Design and Methods: Diabetes was induced in Sprague-Dawley pregnant rats by streptozotocin on day 0 of gestation. Systolic blood pressure, plasma renin activity, renal function, were measured in the offsprings from 1 to 18 months of age. High salt diet experiments were performed at the pre-hypertensive stage and the abundance of tubular sodium transporters was elavuated by western-blot analysis. Kidney tissues were processed for histopathology and glomerular computer-assisted histomorphometry.

Results and Conclusions: We demonstrated that in utero exposure to maternal diabetes induces a salt-sensitive hypertension in the offsprings associated with a decrease in renal function in adulthood. High salt diet experiments show an alteration of renal sodium handling that may be explained by a fetal re-programmation of tubular functions in association or as a result of the inborn nephron deficit induced by in utero exposure to maternal diabetes.