Postnatal modulation of prenatally programmed hypertension by dietary Na and ACE inhibition

The Research Institute for Children and Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana Submitted 11 May 2004 ; accepted in final form 20 September 2004 Adult hypertension in the rat can be programmed experimentally by changes in intrauterine environment. The offspring typically do not become hypertensive until 6 to 8 wk of age, and recent evidence suggests that renal dysfunction may participate in the pathogenesis. The present study was based on the hypothesis that the window for programming extends to the postnatal period in the rat. Adult hypertension was induced by maternal low-protein diet during the second half of gestation. After being weaned at 3 wk, the offspring were exposed to one of the following regimens for the subsequent 3 wk: 1 ) low-Na diet, 2 ) standard Na diet, 3 ) high-Na diet, and 4 ) standard Na diet with enalapril. The pups were followed for 10 wk after discontinuation of the treatments. The brief exposure to low-Na diet or enalapril totally prevented the development of hypertension and the effect lasted throughout the observation period. The development of hyperreninemia, present in the standard Na group at 16 wk of age, was abolished in the low-Na and enalapril groups. Conversely, 3-wk exposure to high-Na diet increased the severity of the later hypertension and did not prevent the hyperreninemia. The findings suggest that there is a period of susceptibility during which prenatally programmed hypertension can be modulated postnatally, possibly coinciding with a critical stage in renal maturation. fetal origins of adult disease; kidney ontogeny; renin-angiotensin system; aldosterone Address for reprint requests and other correspondence: V. Matti Vehaskari, The Research Institute for Children, 200 Henry Clay Ave., New Orleans, LA 70118 (E-mail: vvehas{at}lsuhsc.edu )