Epidemiologic studies have linked intrauterine growth restriction (IUGR) with an increased incidence of cardiovascular disease later in life; reduced cardiomyocyte number in IUGR hearts may underlie such prenatal programming. Our aim was to examine the effect of IUGR, as a result of maternal protein restriction, on the number of cardiomyocytes in the rat heart at birth. Rats were fed either a low-protein diet (LPD) or a normal-protein diet (NPD) during pregnancy. At birth, the offspring were killed and the hearts were immersion-fixed. The number of cardiomyocyte nuclei in the hearts were stereologically determined using an optical disector-fractionator approach. In some litters, cardiomyocytes were enzymatically isolated from freshly excised hearts and the proportion of binucleated cells was determined. Taking into account the number of binucleated cells, the nuclear counts were adjusted to estimate total cardiomyocyte number. Birth weight and heart weight were significantly reduced in the LPD offspring. This was accompanied by a significant reduction in the number of cardiomyocytes per heart in the LPD offspring compared with the NPD offspring (1.18 Ϯ 0.05 ϫ 10 7 and 1.41 Ϯ 0.06 ϫ 10 7 , respectively; p ϭ 0.001). The number of binucleated cardiomyocytes was low (~3%) and equal in both groups. In conclusion, IUGR as a result of maternal protein restriction leads to a reduction in the number of cardiomyocytes per heart. As cardiomyocyte proliferation is rare after birth, it is plausible that this reduction in cardiomyocytes may lead to compromised cardiac function later in life. Epidemiologic studies have shown a link between low birth weight, as a result of intrauterine growth restriction (IUGR), and an increased incidence of cardiovascular disease later in life (1), suggesting that maternal nutrition may affect the long-term disease profile of offspring. IUGR can result from a lack of nutrients, oxygen, or blood supply to the fetus (2). The link to cardiovascular disease later in life in IUGR infants may relate to underdevelopment of vital organs in utero. Indeed, early studies report that a reduced supply of nutrients during early life, prenatal and postnatal, interferes with the rate of cell multiplication in various organs (3) and that the effect is proportionally more deleterious in tissues with a faster rate of cell multiplication (4). Under these circumstances, growth of the brain is generally "spared" by preferential diversion of blood flow to the brain, whereas growth of other organs is usually proportional to body weight (5). For example, a reduced kidney weight in IUGR rats was shown to be associated with decreased nephron endowment (6,7). The effects of IUGR on the heart are less well defined. In IUGR rats that are exposed to maternal protein restriction, a reduced heart weight is often found (8,9). Alternatively, an increased heart weight as a result of a low-protein diet (LPD) has also been documented (10). Whether IUGR influences the number of cardiomyocytes in the heart is still unclear. If IUGR ...

Higher mean glomerular volume and individual glomerular volume heterogeneity mark glomerular stress. Low Nglom is an important determinant of hypertension and renal disease. Many 'missing' nephrons have probably been lost during life, leaving little trace. Additional factors contribute to high rates of hypertension in blacks.

Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension.

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Aim: This study tested the hypothesis that a nephron deficit predisposes rats to salt-sensitive hypertension in adulthood. Methods: Female Wistar-Kyoto rats were fed a low (9%) or a normal (20%) protein diet during pregnancy and lactation. Male, birth-weight-matched offspring were paired. One rat from each pair was perfusion fixed at 4 weeks of age and the other rat at 40 weeks of age. Kidneys were removed and nephron number and total renal filtration surface area (FSA) determined using unbiased stereological techniques. The rats that were allowed to grow to adulthood had tail-cuff systolic blood pressure and body weight determined twice weekly. Between 30 and 40 weeks of age, a normal or a high-salt diet was fed to the rats. Results: The offspring of rats fed the low-protein diet were significantly smaller at birth, and at 4 weeks of age they had a significant reduction in kidney volume, nephron number, and total renal FSA when compared to controls. Tail-cuff systolic blood pressure in the offspring from 4 to 29 weeks of age did not significantly differ between the two groups. Administration of a high-salt diet from 30 to 40 weeks of age led to a significant increase in blood pressure in both dietary treatment groups; however, it was not exacerbated in the rats exposed to the low-protein diet in utero. Conclusions: Maternal protein restriction in rats did not lead to salt-sensitive hypertension. Nephron endowment and FSA did not correlate with blood pressure in adulthood.