Abstract Epidemiological surveys have suggested that intrauterine growth retardation is a risk factor for the de- velopment of hypertension in later life. A rat model of intrauterine growth retardation, induced by maternal low-protein diet during the second half of pregnancy, was used to study the relationship between birth weight and adult hypertension. The offspring were born at term and were allowed to nurse normally until weaned to standard chow at 4 weeks of age. They had 15% lower birth weights than control offspring, with complete catch-up growth by age 4 weeks. Both females and males developed progressively worsening hypertension beginning at 8 weeks. The 11-month survival rate was 69% versus 100% in control animals. During the early stages of the hypertension, plasma creatinine was nor- mal, plasma sodium concentration was slightly higher than that of control animals, plasma renin activity was suppressed, and the males had mild proteinuria. Renal function remained normal throughout the 11-month ob- servation period, but plasma renin activity gradually rose above control values. Angiotensin-converting enzyme inhibition by enalapril, begun at 8 weeks of age, was ef- fective in completely normalizing the blood pressure, but did not totally prevent the extra mortality. Sprague- Dawley and Wistar rat strains developed equally severe hypertension after maternal protein deprivation, despite their different susceptibilities to nephrosclerosis with ag- ing. In conclusion, maternal low-protein diet resulted in low birth weight and adult hypertension in the rat. Pri- mary sodium retention and expanded extracellular vol- ume may be critical factors during the development of the hypertension. Keywords Essential hypertension · Intrauterine growth retardation · Plasma renin activity · Sodium homeostasis · Angiotensin-converting enzyme inhibition Introduction Epidemiological surveys have shown that low birth weight is a risk factor for essential hypertension in later life [1, 2, 3, 4]. The important factor appears to be low weight relative to gestational age, not prematurity [4], suggesting that the in utero environment affecting fetal growth is responsible for the prenatal programming of blood pressure (BP). Interestingly, the inverse relation- ship between birth weight and BP seems to amplify with age, even in the elderly [2]. The association between intrauterine growth retarda- tion and later hypertension has been reproduced experi- mentally in rats by us [5] and others [6, 7], using mater- nal protein deprivation. In our previous report, maternal low-protein diet from gestational age 12 days to term re- sulted in intrauterine growth retardation, catch-up growth during the first 2 weeks of postnatal life, hypertension by 8 weeks of age, and shortened life span in both sexes [5]. The pathogenesis of the prenatally programmed hy- pertension is not known, but several theories have been proposed. Langley-Evans et al. [8, 9] proposed that the effect is mediated through fetal exposure to high mater- nal glucocorticoid levels, leading to permanent alteration of the pituitary-adrenal axis in the offspring. Brenner et al. [10, 11] advanced the theory that essential hyperten- sion, including that associated with intrauterine growth retardation, is the consequence of a reduced total number of nephrons leading to sodium (Na) retention. The role of the renin-angiotensin system is unclear. Both in- creased [7] and unchanged [12] plasma renin activity (PRA) have previously been reported in the experimental rat model, while we found the activity to be low during the early stages of hypertension [5]. The current study was undertaken to further charac- terize the clinical course and to provide insight into the J. Manning · V.M. Vehaskari Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA V.M. Vehaskari ( ✉ ) 200 Henry Clay Avenue, New Orleans, LA 70118, USA Tel.: +1-504-8969238, Fax: +1-504-8969240 Pediatr Nephrol (2001) 16:417–422 © IPNA 2001 ORIGINAL ARTICLE Jennifer Manning · V. Matti Vehaskari Low birth weight-associated adult hypertension in the rat Received: 22 September 2000 / Revised: 8 December 2000 / Accepted: 11 December 2000