Exposure to maternal diabetes induces salt-sensitive hypertension and impairs renal function in adult rat offspring.
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.


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.


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.
Nehiri
Touria
T
Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherche S872, Centre de Recherche des Cordeliers, Paris, France.
Duong Van Huyen
Jean-Paul
JP
Viltard
Mélanie
M
Fassot
Céline
C
Heudes
Didier
D
Freund
Nicole
N
Deschênes
Georges
G
Houillier
Pascal
P
Bruneval
Patrick
P
Lelièvre-Pégorier
Martine
M
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013997:Time Factors
D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; D012083:Renin