Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats

Restriction of maternal protein intake during rat pregnancy produces offspr ing that are hypertensive in adulthood, but the mechanisms are not well und erstood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin -angiotensin system (RAS) and a consequent reduction in nephron number. Pre gnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) di et throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA level s were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II level s were also suppressed in newborn LP (0.079 <plus/minus> 0.002 ng/mg, LP ve rsus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in consci ous, chronically instrumented adult offspring (21 wk) was higher in LP (135 <plus/minus> 1 mm Hg, LP versus 126 +/- 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of gl omeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP ve rsus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 <plus/minus> 0.16 10(6) mum(3), LP versus 1.11 +/- 0.10 10(6) mum(3), NP, p < 0.005); the total volume of all glomeruli per kidney was no t significantly different.. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glom eruli, glomerular enlargement, and hypertension in the adult.