Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood

Abstract

Epidemiological studies have produced evidence that unfavorable intrauterine environments during fetal life may lead to adverse outcomes in adulthood. We have previously shown that a low-sodium diet, given to pregnant rats over the last week of gestation, results in intrauterine growth restriction (IUGR). We hypothesize that pups born with IUGR are more susceptible to the development of hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for organ growth and renal morphogenesis. The adults (12 wk) were evaluated for weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone system (RAAS), and renal function; hearts and kidneys underwent a histological examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR fetuses compared with age-matched controls, whereas the kidney-to-body ratio was unchanged. Systolic blood pressure was elevated in both IUGR male and female adults. Plasma aldosterone levels were not correlated with increased plasma renin activity. Moreover, urinary sodium was decreased, whereas plasma urea was elevated in both males and females, and creatinine levels were augmented only in females, suggesting a glomerular filtration impairment in IUGR. In our model of IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure, alteration of the RAAS, and renal dysfunction are observed in adult life. Differences observed between male and female adults suggest the importance of gender in outcomes in adulthood after IUGR.

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

“…Since Ang II does not cross the placenta (Clark et al 1990), these changes are not dependent on maternal RAAS over-activation observed in low-sodium restricted dams. As young adults (12-week-old), offspring of this IUGR model have been shown to manifest a modest increase in systolic blood pressure, but a disrupted RAAS as well as renal dysfunction, evidenced by reduced glomerular filtration which was not related to a lower number of glomeruli (Battista et al 2002). These modifications were less pronounced in IUGR males, suggesting differing effects between adult males and females following these adverse intrauterine conditions.…”

“…Since we previously showed that IUGR offspring of dams on a low-sodium diet exhibit altered foetal adrenal steroidogenesis (Battista et al 2002, Bibeau et al 2010, we hypothesized that the regulation of aldosterone secretion by adrenal glands is likely influenced by IUGR. The aims of the present study were therefore to characterize the consequence of IUGR on adult male and female adrenal glands (histology, AT 1 R and AT 2 R expression, and steroidogenesis) and, secondly, to determine whether adrenal glands of these IUGR offsprings are vulnerable to the influence of 0 .…”

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats

“…The early period (days 0-7) corresponds to the embryonic phase of development in the rat and in fact embryos only implant at around day 4.5. 7 The mid-gestation period (days [8][9][10][11][12][13][14] largely corresponds to the period of organogenesis, while late gestation (days [15][16][17][18][19][20][21][22] is the period of most rapid growth and differentiation of key structures. By feeding at these targeted periods, it is possible to identify when nutritional programming occurs and this can provide important indicators of potential mechanisms.…”

“…A large number of studies in rats, mice, guinea pigs and sheep have clearly shown that exposure to relatively short periods of undernutrition or endocrine disturbance in fetal life can programme raised blood pressure, glucose intolerance and insulin resistance. [7][8][9] The range of nutritional exposures capable of eliciting programmed responses in the developing offspring is broad, including micronutrient deficiency, [10][11][12] excess of saturated fat 13 and restriction of food intake (global nutrient restriction). 14,15 In the present paper, we report findings from a model of low protein feeding in rat pregnancy.…”

Efeito do hipertiroidismo experimental, induzido em ratas durante a gestação, sobre componentes do sistema renina-angiotensina cardíaco da prole.

“…Battista (2002) Paralelamente, sabe-se que a razão dada pelo peso da placenta/peso corpóreo (PP/PC) corresponde a uma relação crítica, visto que diferentes estudos a relacionam com risco de doença cardiovascular na vida adulta (Barker et al, 1989(Barker et al, , 1990Leon et al, 1998). Neste sentido, se por um lado estudos mostram que o elevado peso da placenta pode refletir um aumento da pressão arterial em crianças (Law et al, 1991;Moore et al, 1996), por outro, achados já mostraram uma relação inversa entre esses dois parâmetros (Willians et al, 1992;Whincup et al, 1995;Taylor et al, 1997 Anjos-Ramos et al, 2006;Kobori et al, 1997Kobori et al, , 1998.…”