Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.

Articles you may be interested inExperimental and theoretical studies of the effect of mass on the dynamics of gas/organic-surface energy transfer A quasiclassical trajectory study of the energy transfer in CO2-rare gas systems Experimental studies of collisional energy transfer from highly vibrationally excited toluene to various bath gases have recently been reported Barker, J. Chern. Phys. 97, 1809 (1992), and references therein]. A quasic1assical trajectory investigation for toluene in argon bath gas at 300 K for initial internal energies E' =41 000, 30000, and 15000 cm -1 is reported here. Collisional energy transfer is almost linearly dependent on E'. Predictions of energy transfer quantities are very sensitive to the average well depth of the assumed individual pairwise potentials, but is less sensitive to the detailed shape. Qualitative and quantitative agreement with experiment is obtained where the overall well depth is physically realistic. Isotope studies using 4°Ar and pseudohelium (4Ar) bath gases indicate that energy transfer is independent of the mass of the bath-gas collider, but perdeuteration increases (6..E2)1I2 by 13% over the undeuterated values. Recently, ToselIi and Barker have reported experimental studies of CET in highly vibrationally excited toluene systems. 17 -20 Other workers have previously studied the same systems. 14 -16 This study reports trajectory investigations of toluene+argon energy transfer and seeks to address some of the following unresolved questions about CET: (1) Cari the energy dependence of R(E,E ' ) be predicted? (2) How important is momentum transfer-mass effects-in the CET mechanism? (3) Does CET "scale" with the potential well depth? (4) Does CET scale with the interatomic repulsive force (i.e., the steepness of the repulsive potentiaI)? Later reports will deal with the temp,erature dependence of CET in toluene+helium systems (paper II),24 and with the interdependence of angular momentum (i.e., rotational energy) transfer and internal-energy transfer. 25 II. THEORYThe first l6 -20 and second 14 moments, RE', 1 and R E I,2 of R(E,E ' ) can be obtained from experiment

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.

No abstract

With the rising prevalence of obesity, particularly among women of reproductive age, it is important to understand the consequences of maternal obesity and nutrient excess on processes underlying development because they may lead to adverse outcomes in offspring. Animal models of maternal fat-rich diets that reflect the dietary intakes of humans in affluent societies have demonstrated the programming of offspring hyperphagia, adiposity, insulin resistance, and hypertension.1,2 Various factors, including elevated blood pressure (BP), insulin resistance, hyperglycemia, elevated plasma glucocorticoids, and leptin, associated with obesity during gestation can affect the development of a fetus.3 These factors can all contribute to a suboptimal intrauterine environment and predispose offspring to an increased risk of obesity and hypertension. There is evidence that the sympathetic nervous system (SNS) may be activated in offspring of fat-fed dams that develop hypertension, 1 but to date no study has shown direct evidence for increased sympathetic vasomotor activity. The adipokine hormone leptin and the gut hormone ghrelin act on neural circuitry of the hypothalamus important for energy homeostasis and the regulation of the SNS. 4,5 We have recently shown that the renal sympathetic nerve activity (RSNA) and BP increases in the first few days of consuming a high-fat diet (HFD) in rabbits can be largely reversed by a leptin antagonist given intracerebroventricularly (ICV). [6][7][8][9] In contrast, ghrelin secreted by the stomach activates arcuate neurons containing neuropeptide Y and agouti-related protein and has been shown to suppress sympathetic activity, decrease BP, and stimulate appetite.10,11 Thus, both leptin and ghrelin may play a key role in the association between obesity and hypertension and may also be involved in the hypertension programmed by a maternal HFD (m-HFD).The purpose of this study was to examine the effect of an m-HFD during development on arterial pressure and RSNA and the central sympathetic effects of leptin and ghrelin in offspring. We used a rabbit model in which an HFD induces elevated BP and RSNA. [6][7][8][9] We hypothesized that offspring exposed to an HFD during development would retain greater deposits of fat and show a selective leptin-resistant phenotype Abstract-Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001),...

Maternal protein restriction leads to a reduction in the number of cardiomyocytes in the rat heart at birth. However, in rats, cardiomyocytes continue to proliferate until about 2 weeks after birth. Hence, this study aimed to examine the effect of maternal protein restriction, on the number of cardiomyocytes in the young rat heart at a time point when the cardiomyocytes have ceased proliferating and are terminally differentiated. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low protein diet (LPD; 8.7% casein) during pregnancy and lactation. Offspring (seven males and seven females per group) were perfusion fixed at 4 weeks of age. Heart volume and total cardiomyocyte number were determined using stereological techniques. At 4 weeks of age, body weights in both male and female LPD offspring were significantly reduced compared with NPD controls whereas relative heart volumes were significantly increased in LPD offspring. Total number of cardiomyocytes was not significantly different between groups. In both groups, there was a significant linear correlation between cardiomyocyte number and heart volume. In conclusion, total cardiomyocyte number in the postproliferative rat heart does not appear to be affected by maternal protein restriction per se but is directly related to heart size. Anat Rec, 293:431-437, 2010. V V C 2010 Wiley-Liss, Inc.

This study examines the effect of maternal protein restriction in rats on levels of cardiac fibrosis, myocardial capillarization, and media:lumen ratio of intramyocardial arteries in adult offspring. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low-protein diet (LPD; 8.7% casein) during pregnancy and lactation. Female offspring (seven per group) were weaned at 4 wk of age and grown to adulthood. At 24 wk of age, the offspring were perfusion fixed. Cardiac fibrosis and media:lumen ratio of intramyocardial arterioles was assessed using image analysis and cardiac capillarization was stereologically investigated. Body weights at 2 and 24 wk of age were significantly reduced (31% and 8%, respectively) in the LPD offspring; however, heart size was not different at 24 wk. Importantly by adulthood, there was a significant 15% increase in left ventricular interstitial fibrosis in LPD offspring. There were no differences in levels of perivascular fibrosis, myocardial capillarization, or in the media:lumen ratio of intramyocardial arteries between groups. Because cardiac fibrosis is associated with impaired cardiac contractility and arrhythmia, our results suggest that induction of interstitial fibrosis may contribute to the increased cardiac disease in adult subjects who were exposed to an adverse intrauterine environment. M any epidemiologic studies have shown that subjects exposed to perturbations in early development have an increased incidence of cardiovascular disease later in life (1-3). It is likely that an adverse intrauterine environment may permanently reduce the numbers of cells/functional units in vital organs, which in turn will affect postnatal organ function. Recent experimental studies of reduced nephron endowment in kidneys, as a result of maternal protein restriction, and subsequent detrimental effects on renal function later in life support this concept (4); whether this is the case in the heart has not yet been elucidated. Interestingly in a recent study in our laboratory, we found that maternal protein restriction throughout pregnancy in rats leads to a reduced heart size and a concomitant decrease in the number of cardiomyocytes (5). Because cardiomyocytes in general cease proliferating soon after birth, with postnatal growth of the heart predominantly due to cardiomyocyte hypertrophy (6), these findings could have important adverse implications on the structure and function of the heart later in life. We postulate that a decrease in the total number of cardiomyocytes in neonatal hearts will limit the capacity for physiologic cardiac growth in adulthood. We propose that when cardiomyocytes reach their limits of hypertrophy, further enlargement of the heart will then occur through increased deposition of extracellular matrix leading to cardiac fibrosis.Indeed, accumulation of extracellular matrix structural proteins in the heart adversely affects myocardial viscoelasticity (7,8) with accumulation of fibrillar collagen leading to cardiac dysfunction (9...

No abstract