Association of Birth Weight with Cardiovascular Parameters in Adult Rats During Baseline and Stressed Conditions

Schreuder, Michiel F.; Fodor, Mariann; Wijk, J. A. E. van; Waal, Henriëtte A. Delemarre-van de

doi:10.1203/01.pdr.0000190576.08501.df

Cited by 31 publications

(29 citation statements)

References 44 publications

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“…Because the glomerular volume is related to glomerular number, which is associated with birth weight, there is an indirect link between birth weight and proteinuria. Nephron endowment and raised BP in adult life have been linked (14), and we have shown a rise in systolic BP in the described model of IUGR (43).…”

Section: Discussionmentioning

confidence: 56%

Glomerular Number and Function Are Influenced by Spontaneous and Induced Low Birth Weight in Rats

Schreuder

Nyengaard

Fodor

et al. 2005

Journal of the American Society of Nephrology

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A link exists between low birth weight and diseases in adulthood, such as hypertension, cardiovascular disease, and insulin resistance. Intrauterine growth restriction (IUGR) has been used to explain this association and has been shown to lead to a nephron endowment in humans. A reduction in glomerular number has been described in animal models with induced low birth weight as well but not in animals with spontaneous low birth weight. It therefore is debatable whether the models are suitable. The effect on glomerular number and size was studied in rats with naturally occurring IUGR and experimental IUGR, induced by bilateral uterine artery ligation. Design-based stereologic methods were used. Urinary protein excretion was determined as a measure of renal damage. Results showed a decrease of approximately 20% in glomerular number in both groups of IUGR (control 35,400, naturally occurring IUGR 30,900, and experimental IUGR 28,000 glomeruli per kidney). Mean glomerular volume was increased in both IUGR groups, which was associated with an increased proteinuria. It is concluded that IUGR leads to a nephron endowment with a compensatory glomerular enlargement. This compensation is associated with more proteinuria in the long run. Uterine artery ligation in the pregnant rat is a suitable model to study the effects of IUGR on the kidney. L ow birth weight (LBW) is associated with an increased risk for chronic diseases such as hypertension, cardiovascular disease, and insulin resistance and diabetes in later life (1-5). Even though the causal pathways are not yet understood, the "fetal origins hypothesis" (1) suggests that an insult during fetal life that leads to intrauterine growth restriction (IUGR) not only results in LBW but also reprograms the development of organs. This reprogramming may have beneficial effects in the suboptimal uterine environment but predisposes to long-term health problems.The number of nephrons in humans is determined in utero, with no new nephrons being formed after the 36th week of gestation (6 -8). IUGR leads to a lower number of glomeruli in humans (9 -11), which may predispose to development of glomerular and eventually systemic hypertension in later life according to the hyperfiltration theory (12)(13)(14). A relationship between low nephron number and raised BP has been confirmed in patients with "essential" hypertension: Compared with individuals with normal BP, patients with hypertension had fewer glomeruli at autopsy (15).Various animal models support the association between LBW and a low glomerular number (16 -20), but a correlation between naturally occurring LBW and nephron endowment has not been shown consistently (21). This suggests that the results may be more due to the method of obtaining LBW than the LBW per se and therefore do not provide a suitable model.It is important to have an animal model that closely resembles the cause of IUGR in humans to study the association between LBW and kidney development. We used a model of uterine artery ligation in the pregnant rat resem...

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Section: Discussionmentioning

confidence: 56%

Glomerular Number and Function Are Influenced by Spontaneous and Induced Low Birth Weight in Rats

Schreuder

Nyengaard

Fodor

et al. 2005

Journal of the American Society of Nephrology

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“…Tonkiss et al 26 observed an increased blood pressure response to stress in IUGR rats and suggested that the large and frequently positive findings obtained with tail cuff measurements could, to some extent, reflect an effect of programming to increase the blood pressure response to stress. A tendency toward an increased blood pressure response to stress was also apparent in 1 other study of IUGR rats 27 but absent in another. 25 Although we did not observe any effect of maternal eNOS genotype on the blood pressure response to handling and disturbance, we did observe an effect of maternal eNOS genotype on other aspects of behavior.…”

Section: Van Vliet and Chafementioning

confidence: 66%

“…Maternal eNOS Genotype Affects Offspring BPrestriction during pregnancy 26 ; an 8-, 6-, and 4-mm Hg increase in nocturnal systolic, mean, and pulse pressures, respectively, in a model of bilateral uterine artery ligation 27 ; and Յ10-and 14-mm Hg increases in diastolic and systolic pressures in offspring of mothers fed a high-fat diet during pregnancy 28,29 ). The available data suggest that, when telemetry methods are used to minimize potential stress-induced artifacts, IUGR is associated with a statistically significant though modest impact on offspring blood pressure.…”

Section: Van Vliet and Chafementioning

confidence: 99%

Maternal Endothelial Nitric Oxide Synthase Genotype Influences Offspring Blood Pressure and Activity in Mice

Vliet

Chafe

2007

Hypertension

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Abstract-Deficiencies in maternal endothelial NO synthase (eNOS) have been associated with pregnancy complications, intrauterine growth retardation, and altered vascular function in offspring. In the present study, we investigated the influence of the maternal eNOS genotype on offspring's blood pressure, heart rate, and locomotor activity. The effect of maternal eNOS genotype was made by comparing telemetered blood pressure and activity between 2 groups of 13-to 16-week-old male heterozygous eNOS knockout mice, 1 produced by a cross of eNOS knockout (eNOS Ϫ/Ϫ ) mothers and wild-type (eNOS ϩ/ϩ ) fathers (eNOS ϩ/ϪMAT offspring, Nϭ11), the other by a cross of eNOS ϩ/ϩ mothers and eNOS Ϫ/Ϫ fathers (eNOS ϩ/ϪPAT offspring, Nϭ10). Data were also collected for homozygous eNOS Ϫ/Ϫ and eNOS ϩ/ϩ mice (Nϭ15 each). Heterozygous eNOS knockout mice exhibited blood pressures that were intermediate to the eNOS ϩ/ϩ and eNOS Ϫ/Ϫ groups. Relative to eNOS ϩ/ϪPAT mice, eNOS ϩ/ϪMAT mice exhibited significant increases in nocturnal diastolic arterial pressure and diurnal variations (dark-light difference) in systolic, mean, and diastolic arterial pressure. In addition, indices of spontaneous nocturnal locomotor activity, including both the proportion of time spent active and the intensity of activity when active, were also significantly increased. Heart rate did not differ between the groups. Our results suggest that the maternal eNOS genotype influences both blood pressure and behavior of offspring, possibly as a consequence of developmental programming associated with intrauterine growth retardation. Key Words: experimental hypertension Ⅲ pregnancy Ⅲ developmental programming Ⅲ maternal environment Ⅲ hyperactivity Ⅲ knockout mice Ⅲ telemetry Ⅲ nitric oxide T he characteristics of many physiological systems are influenced by the conditions prevailing during development. 1 Perturbations of the maternal environment that lead to intrauterine growth retardation (IUGR) can have a marked impact on the grown offspring, including increased cardiovascular risk factors (eg, blood pressure and insulin resistance 1,2 ) and reduced adult life span. 3 A wide range of experimental interventions have been used to provoke developmental programming, including disturbances in maternal nutrition (eg, undernutrition and nutritional imbalances 4 ), restriction of uterine blood flow, 5 and the administration of drugs (eg, glucocorticoids 2 and NO synthase inhibitors 6,7 ).A relatively unexplored possibility is that developmental programming could also occur as a consequence of maternal genotype. Maternal endothelial NO synthase (eNOS) is a potential candidate in this regard, because eNOS has been shown to play an important role in the regulation of uterine blood flow, 8,9 and IUGR has been observed in rats treated with inhibitors of NO synthase 6,7 and in mice with targeted deletion of the eNOS gene (eNOS Ϫ/Ϫ ) 8,10 . In humans, polymorphisms of the eNOS gene are common and are associated with endothelial dysfunction, 11-13 increased uterine artery resistan...

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“…This is of interest since it contrasts with the effect of intrauterine growth retardation induced by uterine artery ligation 4 days before term (22) and may be indicative that blood pressure remains lower in the longer term in NR offspring. One alternative explanation is that they are developing a gradual rise in blood volume, thereby promoting peripheral vasodilatation.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

Brennan

Kaufman²,

Reynolds³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism, and receptor expression. Since the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control-fed mothers and eight nutrient-restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient-restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE2, with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development and decreased blood pressure.kidney; nutrient restriction; offspring; prostaglandins MATERNAL NUTRIENT RESTRICTION during pregnancy has been previously shown to affect the renal development of the offspring. In the sheep, nutrient restriction targeted to the period of early kidney development subsequently increases organ size as well as affecting kidney shape and promotes glucocorticoid receptor (GCR) mRNA abundance (32). Global nutrient restriction (9) and protein restriction in particular can both reduce the total number of nephrons formed in developing rat kidneys, but this does not necessarily result in raised blood pressure in the offspring (11). The mechanisms by which maternal nutritional manipulation acts to compromise fetal development and ultimately adult health remain uncertain. It has been proposed that this is dependent in part on increased maternal corticosterone concentrations acting directly on the fetus (16). This proposal is supported by the finding that maternal administration of dexamethasone, which crosses the placenta to the fetus during pregnancy, can cause similar cardiovascular outcomes as observed with maternal food deprivation (40); indeed, dexamethasone administration also results in reduced maternal food consumption, suggesting a behavioural effect on appetite (37, 40). Recently, it has been shown that a transient increase in maternal corticosterone on days 14 and 15 of pregnancy in rats can impair development of the intra-...

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Association of Birth Weight with Cardiovascular Parameters in Adult Rats During Baseline and Stressed Conditions

Cited by 31 publications

References 44 publications

Glomerular Number and Function Are Influenced by Spontaneous and Induced Low Birth Weight in Rats

Glomerular Number and Function Are Influenced by Spontaneous and Induced Low Birth Weight in Rats

Maternal Endothelial Nitric Oxide Synthase Genotype Influences Offspring Blood Pressure and Activity in Mice

Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring

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