Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats.
Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. 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. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet 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 levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 +/- 0.002 ng/mg, LP versus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 +/- 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 glomeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP versus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 +/- 0.16 10(6) microm(3), LP versus 1.11 +/- 0.10 10(6) microm(3), NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult.
Division of Nephrology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, Oregon 97201-3098, U.S.A. woodsl@ohsu.edu
L L
LL
Woods
J R
JR
Ingelfinger
J R
JR
Nyengaard
R
R
Rasch
D000818:Animals; D000831:Animals, Newborn; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000033:anatomy & histology / Q000503:physiopathology; D009747:Nutritional Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System
D004044:Dietary Proteins