Exposure to Maternal Diabetes Induces Salt-Sensitive Hypertension and Impairs Renal Function in Adult Rat Offspring

• DOI: 10.2337/db07-0780
• Publication Date: 2008-04-29T00:55:28Z
• Authors: Touria Nehiri; Jean-Paul Duong V...; Mélanie Viltard; Céline Fassot; Didier Heudes; Nicole Freund; Georges Deschênes; Pascal Houillier; Patrick Bruneval; Martine Lelièvre...
• Keywords: 0301 basic medicine; Complications; Time Factors; [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; [SDV]Life Sciences [q-bio]; Blotting, Western; Pregnancy in Diabetics; Blood Pressure; Kidney; Diabetes Mellitus, Experimental; Rats, Sprague-Dawley; 03 medical and health sciences; Pregnancy; Renin; [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; Animals; Sodium Chloride, Dietary; Epithelial Sodium Channels; 2. Zero hunger; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Immunohistochemistry; Rats; 3. Good health; [SDV] Life Sciences [q-bio]; Animals, Newborn; Hypertension; Female; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Glomerular Filtration Rate

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, and renal function were measured in the offspring from 1 to 18 months of age. High-salt diet experiments were performed at the prehypertensive stage, and the abundance of tubular sodium transporters was evaluated 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 offspring 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 reprogramming of tubular functions in association or as a result of the inborn nephron deficit induced by in utero exposure to maternal diabetes.