Manning. Kidney angiotensin and angiotensin receptor expression in prenatally programmed hypertension. Am J Physiol Renal Physiol 287: F262-F267, 2004. First published April 20, 2004 10.1152/ajprenal.00055.2004.-Adult hypertension may be programmed by the prenatal environment in humans and in experimental animals. The potential role of the intrarenal renin-angiotensin system (RAS) in prenatally programmed hypertension was investigated. Hypertension in rat offspring was induced by maternal protein restriction during pregnancy. The offspring were studied on day 1 of life and immediately preceding the development of hypertension on day 28. ANG I and II contents were determined by radioimmunoassy. Angiotensin receptor protein and mRNA levels were quantified by immunoblotting and real-time RT-PCR, respectively. Plasma and kidney ANG I and II were unchanged in the offspring from low-protein pregnancies (LP). ANG II type 1 receptor (AT1R) protein abundance was low in the newborn LP kidney (P Ͻ 0.05) but rose above control values by 28 days of age (P Ͻ 0.05); the rise was associated with an increase in AT1R subtype A (P Ͻ 0.01), but not subtype B, mRNA level. ANG II type 2 receptor protein expression was decreased on day 1 (P Ͻ 0.05) and increased on day 28 (P Ͻ 0.05) in LP kidneys. The results show that prenatal programming of hypertension is associated with an abnormal pattern of intrarenal RAS ontogeny that may play a pathogenetic role, for instance, by constitutively altering renal hemodynamics or Na reabsorption.fetal origins of adult disease; kidney ontogeny; low-protein diet THE CONCEPT OF "PRENATAL PROGRAMMING of adult disease" refers to modulation of future adult phenotype by nongenetic environmental factors in utero. Programming of hypertension is the most extensively studied example of prenatal programming. Both epidemiological data (2,7,8,19,24) and experimental studies (18,22,36,39) have provided strong evidence that prenatal environment can modify adult blood pressure. The development of hypertension has been linked to intrauterine growth retardation in humans (1,2,7,8,19,24) and rats (18,22,36,39), suggesting a common mechanism despite species differences. In experimental animals, maternal protein (18,36,39) and calorie (38) restriction and maternal dexamethasone treatment (9, 29) have been used to program adult hypertension in offspring.The mechanisms of the development of hypertension in offspring are unclear. Although other mechanisms such as a disordered hypothalamic-pituitary-adrenal axis have been proposed (34), there is strong evidence to support a role for the kidney in the pathogenesis. Several studies have documented a deficit in the total number of nephrons in experimental programming of hypertension (17,36,39). A recent study of humans with essential hypertension also reported a decrease in the nephron count (15), consistent with the hypothesis that congenital nephron deficit has a role in essential hypertension (4). On the other hand, we reported upregulation in renal sodium (Na) transporter...