Published online before print May 12, 2008, doi: 10.1161/HYPERTENSIONAHA.107.092890
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(Hypertension. 2008;52:44.)
© 2008 American Heart Association, Inc.
Brief Reviews |
Developmental Programming of Hypertension
Insight From Animal Models of Nutritional Manipulation
From the Department of Physiology, University of Mississippi Medical Center, Jackson.
Correspondence to Barbara T. Alexander, Department of Physiology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail balexander{at}physiology.umsmed.edu
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Introduction |
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 Top Introduction Animal Models of Nutritional...Mechanisms of Developmental...References |
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Low birth weight (LBW), defined as a birth weight of
2.5 kg at term, is a major health issue within the United States today. The risk for LBW is greater within the black population than the white, with a greater percentage of LBW occurring within the southern United States relative to other parts of the country.1 Infants born small for gestational age not only have a greater risk for survival at birth2,3 but, based on numerous epidemiological studies, face long-term consequences, such as increased risk for development of hypertension, cardiovascular disease, diabetes, and other health problems.4–6 Barker7 first proposed that an adverse environmental stimulus experienced during a critical period of fetal development leads to slow fetal growth and permanent structural and physiological changes in the fetus predisposing it to increased risk for the development of hypertension and cardiovascular disease. Investigators using animal models to induce an adverse fetal environment and mimic the human condition of slow fetal growth are providing convincing evidence to support the concept of developmental programming of adult disease.8–17 Although there is compelling epidemiological and experimental data that suggest that cardiovascular diseases such as hypertension may be programmed in utero, the underlying pathophysiological mechanisms remain unclear. Investigators use unique animal models of nutritional manipulation to induce slow fetal growth to examine the mechanisms linking birth weight and chronic adult disease, such as hypertension. In this review, we discuss alterations in potential mechanistic pathways that evolve in response to fetal insult and lead to the developmental programming of hypertension, highlighting insight provided by animal models of nutritional manipulation. |
Animal Models of Nutritional Manipulation During Fetal Life |
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TopIntroductionAnimal Models of Nutritional...Mechanisms of Developmental...References |
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Nutritional restriction is one of the most common experimental methods of fetal insult used for investigation into the mechanisms of programmed hypertension and was one of the first to demonstrate that exposure to an adverse environment in utero leads to marked structural and physiological alterations.17 Importantly, this method of fetal insult was also one of the first to demonstrate that timing of the insult is critical to the programming response, with a reduction in nephron number observed when the nutritional insult coincides with the nephrogenic period.8,13,18–21 Observations linking nutritional restriction during gestation with elevated blood pressure in offspring have been controversial.21–24 In the rat, variations in dietary nutrient and protein balance are reported to contribute to differing blood pressure responses in offspring,22 with postnatal influences such as excessive weight gain exacerbating the effect.25 In humans, childhood growth is also a strong determinant of adult blood pressure demonstrating the importance of the postnatal environment on adult disease.26 In the sheep model of nutrient restriction, birth weight rather than maternal diet may play a more critical role in the blood pressure response,23 with maternal body composition at the time of conception also critical to cardiovascular outcome.21 Animal models of reduced uteroplacental perfusion during late gestation also lead to an environment of undernutrition and hypertension in the intrauterine growth-restricted (IUGR) offspring.10,11 Contention exists with regard to the reproducibility of these models.27 However, consistent observations of IUGR are reported by numerous investigators10–12,28,29; moreover, similar phenotypic outcomes, such as a reduction in nephron number, have been observed in response to placental insufficiency, an observation that is not species specific.29–32 Overnutrition as a nutritional insult during fetal life also programs metabolic and cardiovascular dysfunction,33–35 implications critical because of the increased prevalence of obesity.36
Importantly, these models of nutritional manipulation demonstrate characteristics reflective of the human condition of LBW, including marked increases in blood pressure10–15,17,19,35,37,38 and reduced nephron number.13,15,18,28,29,39 In humans, nephron number is directly correlated with birth weight and inversely correlated with blood pressure.40 Thus, models of nutritional insult, whether induced by direct manipulation of the gestational diet or through a reduction in uteroplacental perfusion, serve as relevant pathophysiological models for investigation into the mechanisms linking birth weight and blood pressure and provide the basis for the discussion of potential mechanistic pathways presented in this review.
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Mechanisms of Developmental Programming of Hypertension |
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TopIntroductionAnimal Models of Nutritional...Mechanisms of Developmental...References |
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Hormones
Hormones are known to play a critical role in the proper development and growth of fetal tissues,41 and it is well documented that alterations in the intrauterine hormonal environment can lead to long-term effects on fetal outcome and cardiovascular health.42–46 In experimental studies, inappropriate exposure to testosterone during gestation results in IUGR,44 impaired insulin sensitivity,45 and cardiovascular dysfunction,46 demonstrating a critical role for sex hormones in the developmental programming of adult cardiovascular disease.
Models of developmental programming exhibit sex differences with severity of the fetal insult critical to the adult phenotypic outcome.18,47 Although severe protein restriction during gestation in the rat leads to hypertension and changes in renal structure in both male and female offspring,15,18 moderate protein restriction during gestation in the rat leads to marked increases in blood pressure and a reduction in nephron number in male but not female offspring.15,18,47 Therefore, female offspring appear to be protected from an unfavorable phenotypic outcome in response to a moderate undernutritional insult in utero. However, in models of programming induced by maternal diet-induced obesity, the prevalence for hypertension is greater35 or present only38 in female offspring, indicating that sex differences in the sensitivity to nutritional manipulation are insult specific. Sex differences in adult blood pressure are not observed in models of undernutrition programmed by placental insufficiency in the rat when assessed indirectly by the tail cuff in conscious, restrained animals.11,48 Conversely, sex differences in adult blood pressure are observed when measured directly by telemetry49,50; blood pressure after puberty is stabilized to normotensive levels in female IUGR, yet is further increased in male IUGR.49,50 Castration abolishes hypertension in male IUGR49; ovariectomy induces hypertension in female IUGR rats, an effect reverted by hormonal replacement therapy.50 Thus, sex differences in the blood pressure response to placental insufficiency in IUGR offspring indicate a potential role for sex hormones in mediating sex differences in the postnatal blood pressure response to fetal insult (Figure 1).
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Sexual dimorphism is observed in human essential hypertension and in experimental models of hypertension,51–54 with a role for sex hormone involvement strongly indicated. Hypertension is less prevalent in premenopausal women as compared with age-matched men. However, after menopause, the risk of hypertension increases with age,51,52 suggesting that whereas the ovaries are functional, women have a lower risk for hypertension and cardiovascular disease than men. Experimental studies suggest that sex hormones play a mechanistic role in blood pressure control. Ovariectomy exacerbates the existing hypertension in female rats in some experimental models of hypertension,53,54 suggesting an important role for estradiol in blood pressure regulation. Androgens exacerbate hypertension in the male spontaneously hypertensive rat55; castration reduces blood pressure in the male spontaneously hypertensive rat,56 thus indicating a role for androgens. Thus, sex hormones appear to contribute to sex differences in adult blood pressure regulation. Whether sex hormones are altered in LBW individuals is controversial.57–60 Moreover, few investigators have reported whether adult sex hormones are altered in response to fetal insult,61–66 nor have they examined the direct effect of sex hormones on postnatal hypertension in experimental models of developmental programming. Thus, the exact mechanism(s) by which sex hormones contribute to the developmental programming of blood pressure regulation has not been clearly elucidated but may involve modulation of systems critical to the long-term control of blood pressure regulation.
The Renin-Angiotensin System
The renin-angiotensin system (RAS) is a major regulator of blood pressure control and volume homeostasis.67 Numerous studies indicate that the RAS plays an important role in the etiology of hypertension programmed by in utero insult15,49,50,68–72 (Figure 1). A critical role for the central RAS is indicated in hypertension programmed in response to maternal undernutrition in the rat with marked increases in angiotensin (Ang) type 1 receptor (AT1R) expression observed in areas of the brain critical to cardiovascular regulation73 (Figure 1). In the kidneys, temporal alterations in the RAS occur in response to fetal insult. A reduction in intrarenal renin and Ang II is observed at birth in response to maternal protein restriction in the rat15 followed by postnatal upregulation of the renal AT1R.70,72 In addition, inappropriate activation of the peripheral RAS, demonstrated by a marked increase in plasma renin activity, occurs after the development of hypertension.68,69 Importantly, hypertension is abolished by systemic blockade of the RAS,68,69,71 indicating that the RAS contributes to hypertension programmed in response to maternal nutrient restriction. In a model of undernutrition induced by placental insufficiency, temporal alterations in the renal RAS are also observed with renal angiotensinogen and renin mRNA expression suppressed at birth but markedly elevated in adulthood.74 Unlike models of maternal nutrient restriction, renal AT1R and Ang II expression, as well as inappropriate activation of the peripheral RAS, are not observed,4950,74; yet, the importance of the RAS is indicated as hypertension is abolished by RAS blockade.49 Although the contribution of the RAS to the development of hypertension is not clearly defined, it may involve an increased responsiveness to Ang II. Androgens can augment renal vascular responses to Ang II.75 Elevated levels of testosterone are observed in male IUGR programmed in response to placental insufficiency.49 Therefore, elevated levels of adult testosterone may be one mechanism by which sensitivity to Ang II is increased and may also contribute to the enhanced intrarenal renin and angiotensinogen mRNA expression observed in adult male IUGR.76
Modulation of the RAS by estradiol may also contribute to sex differences in hypertension programmed by fetal insult. Estradiol is reported to downregulate tissue angiotensin-converting enzyme (ACE)77 and AT1R mRNA expression,78 suggesting that estradiol may reduce Ang II, a potent vasoconstrictor peptide critical for blood pressure regulation.67,79 Estradiol may also alter the ACE2-dependent pathway,80 which generates Ang 1-7, a negative regulator of the vasoconstrictor effects of Ang II.79 Modulation of the RAS by estradiol may be one mechanism by which sex hormones play a protective role against an increase in blood pressure in adult female IUGR offspring in a model of undernutrition induced by placental insufficiency. Hypertension is induced by ovariectomy in female IUGR but not female control offspring.50 ACE inhibition abolishes ovariectomy-induced hypertension,50 suggesting a critical role for the RAS. Normotensive adult female IUGR offspring exhibit a significant elevation in renal ACE2 mRNA expression that is decreased by ovariectomy with no effect observed in adult female control.50 Thus, loss of estradiol may decrease the vasodilator effect provided by the ACE2 pathway leading to an increase in blood pressure in adult female IUGR after ovariectomy. Therefore, permanent alterations in the RAS occur in response to fetal insult and contribute to the development of hypertension; modulation of the RAS by sex hormones is one mechanism that may contribute to sex differences in programmed hypertension (Figure 1).
The Renal Nerves
Many known regulatory mechanisms control sodium balance, and alterations in sympathetic activity have sustained effects to reduce pressure natriuresis and result in long-term changes in arterial pressure.81,82 However, whether sympathetic function contributes to hypertension in LBW individuals is controversial.83–86 Circulating levels of catecholamines, neurotransmitters that serve as an indirect marker of sympathetic nerve outflow, are increased in response to fetal undernutrition in models of developmental programming induced by both gestational protein restriction87 and also placental insufficiency in the rat88 and sheep.89 The importance of the renal nerves in the etiology of hypertension programmed by in utero insult was demonstrated recently whereby renal denervation normalized arterial pressure in adult male IUGR offspring in a model of placental insufficiency with no significant effect on blood pressure in adult control offspring.90 Therefore, these findings indicate that the renal nerves play an important role in the etiology of hypertension programmed by fetal undernutrition induced by placental insufficiency (Figure 1). Increased sympathetic outflow including sustained increases in renal sympathetic nerve activity can also occur as a result of the actions of Ang II in regions of the brain critical for cardiovascular regulation.91 Thus, central activation of the RAS leading to an increase in renal sympathetic nerve activity may induce altered renal nerve development in IUGR offspring resulting in hypertension.
Oxidative Stress
A decrease in bioavailability of antioxidants leading to an increase in oxidative stress is indicated to play an important role in essential and experimental hypertension.92,93 Oxidative stress is increased in LBW children,94 suggesting that alterations in oxidant status may contribute to hypertension programmed in response to fetal insult. In experimental models of in utero exposure to undernutrition, hypertension is abolished by administration of the superoxide dismutase mimetic Tempol95 or the lipid peroxidation inhibitor lazaroid,96 implicating an important role for oxidative stress (Figure 1). Ang II stimulates oxidative stress through its AT1R.97 Thus, upregulation of renal AT1R and inappropriate activation of the RAS may serve as stimuli for increased oxidative stress in the developmental programming of hypertension.
Nephron Number
A reduction in nephron number is a phenotypic outcome commonly observed in the fetal response to gestational insult in experimental models of undernutrition induced by maternal nutrient restriction8,14,15,20,21,98 and placental insufficiency.29–32 A reduction in nephron number leading to a reduction in renal excretory function is suggested to serve as a mechanism in the developmental programming of hypertension. Whether a reduced nephron complement could lead to hypertension was demonstrated in a study whereby removal of 1 kidney during the nephrogenic period in the rat led to adult hypertension.99 However, recent findings indicate that a reduction in nephron number is not always critical to the developmental programming of hypertension. A maternal diet rich in fat does not alter the nephron number in offspring.100 Furthermore, an increase in glomerular volume is often observed in conjunction with a reduced nephron number.18 Glomerular filtration rate is not decreased in a rat models of maternal protein restriction15 or placental insufficiency.10 Thus, compensatory hyperfiltration may occur in response to fewer nephrons at birth, resulting in preservation of the glomerular filtration rate,10,15,98 suggesting that factors other than a reduced nephron complement contribute to the etiology of hypertension programmed by in utero insult. Numerous factors including intrarenal sodium transport defects and/or abnormalities in the extrarenal control systems that regulate kidney function can mediate a reduction in renal sodium excretory function observed in hypertension.101 Thus, a sodium retaining defect not mediated by alterations in the filtered load of sodium may be the main contributor to a reduction in pressure natriuresis and hypertension programmed in response to adverse developmental influences (Figure 2). Whether a reduction in nephron number leading to a decrease in glomerular filtration rate contributes to hypertension programmed in response to fetal insult is unclear. Nevertheless, a reduction in nephron complement may diminish resistance to renal damage in adult life leading to an increased susceptibility to renal disease.
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Susceptibility to Renal Disease
Progression of renal injury and disease is closely linked to hypertension. It is well established that the kidney exhibits increased vulnerability to fetal insult as evidenced by the association of reduced nephron number with IUGR in animal models of fetal nutrient manipulation.8,14,15,20,21,29–32,98 However, recent studies indicate that susceptibility to renal disease is greater in LBW individuals102,103 with implications for a gender bias and a protective role for estradiol in women.104 Hypertension associated with an increase in urinary albuminuria,105 glomerulosclerosis, and histological determinants of renal damage106,107 is observed in offspring of nutrient-restricted dams. Hypertension, proteinuria, and glomerulosclerosis are reduced by long-term postnatal L-arginine supplementation; however, evidence of renal damage persists.106 Therefore, these studies indicate that increased susceptibility to renal damage is not just the result of hypertension but may have an origin in fetal life. Furthermore, a reduction in nephron number at birth in conjunction with an increase in glomerular size and compensatory hyperfiltration may contribute to an increased susceptibility to renal injury and enhance the later development of hypertension in LBW individuals (Figure 1).
Perspectives
Insight provided by animal models of nutritional manipulation during fetal life suggests that slow fetal growth leads to alterations in the normal regulatory systems involved in the long-term control of blood pressure regulation. The pathogenesis of hypertension programmed by in utero insult is multifactorial and may involve intrinsic intrarenal defects or alterations in extrarenal regulatory systems critical to renal sodium excretory function. Moreover, a role for sex steroids is also demonstrated. Understanding the complexity of the fetal programming of adult disease may lead to preventive measures and early detection of cardiovascular risk in LBW individuals.
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Acknowledgments |
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Sources of Funding
B.T.A. is supported by National Institutes of Health grants HL074927 and HL51971.
Disclosures
None.
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Footnotes |
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This paper was sent to Ernesto L. Schiffrin, associate editor, for review by expert referees, editorial decision, and final disposition.
Received November 29, 2007; first decision December 22, 2007; accepted April 14, 2008.
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References |
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TopIntroductionAnimal Models of Nutritional...Mechanisms of Developmental...References |
|---|
1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S. Births: final data for 2004. Natl Vital Stat Rep. 2006; 55: 1–101.[Medline] [Order article via Infotrieve]
2. Bernstein IGS, Reed KL. Intrauterine Growth Restriction. Philadelphia, PA: Churchil Livingstone; 2002.
3. Baschat AA, Hecher K. Fetal growth restriction due to placental disease. Semin Perinatol. 2004; 28: 67–80.[CrossRef][Medline] [Order article via Infotrieve]
4. Huxley RR, Shiell AW, Law CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens. 2000; 18: 815–831.[CrossRef][Medline] [Order article via Infotrieve]
5. Syddall HE, Sayer AA, Simmonds SJ, Osmond C, Cox V, Dennison EM, Barker DJ, Cooper C. Birth weight, infant weight gain, and cause-specific mortality: the Hertfordshire Cohort Study. Am J Epidemiol. 2005; 161: 1074–1080.
6. Newsome CA, Shiell AW, Fall CH, Phillips DI, Shier R, Law CM. Is birth weight related to later glucose and insulin metabolism?–a systematic review. Diabet Med. 2003; 20: 339–348.[CrossRef][Medline] [Order article via Infotrieve]
7. Barker D. Mother, Babies, and Disease in Later Life. London, United Kingdom: BMJ Publishing Group; 1994.
8. Symonds ME, Stephenson T, Gardner DS, Budge H. Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows. Reprod Fertil Dev. 2007; 19: 53–63.[CrossRef][Medline] [Order article via Infotrieve]
9. Dodic M, Abouantoun T, O'Connor A, Wintour EM, Moritz KM. Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension. 2002; 40: 729–734.
10. Alexander BT. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension. 2003; 41: 457–462.
11. Baserga M, Hale MA, Wang ZM, Yu X, Callaway CW, McKnight RA, Lane RH. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R1943–R1955.
12. Schreuder MF, van Wijk JA, Delemarre-van de Waal HA. Intrauterine growth restriction increases blood pressure and central pulse pressure measured with telemetry in aging rats. J Hypertens. 2006; 24: 1337–1343.[Medline] [Order article via Infotrieve]
13. Langley-Evans SC, Welham SJ, Jackson AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci. 1999; 64: 965–974.[CrossRef][Medline] [Order article via Infotrieve]
14. Vehaskari VM, Aviles DH, Manning J. Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59: 238–245.[Medline] [Order article via Infotrieve]
15. Woods LL, Ingelfinger JR, Nyengaard JR, Rasch R. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49: 460–467.[Medline] [Order article via Infotrieve]
16. Guron G. Renal haemodynamics and function in weanling rats treated with enalapril from birth. Clin Exp Pharmacol Physiol. 2005; 32: 865–870.[CrossRef][Medline] [Order article via Infotrieve]
17. Langley-Evans SC, Phillips GJ, Jackson AA. In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr. 1994; 13: 319–324.[CrossRef][Medline] [Order article via Infotrieve]
18. Woods LL, Weeks DA, Rasch R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004; 65: 1339–1348.[CrossRef][Medline] [Order article via Infotrieve]
19. Langley-Evans SC, Welham SJ, Sherman RC, Jackson AA. Weanling rats exposed to maternal low-protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clin Sci (Lond). 1996; 91: 607–615.[Medline] [Order article via Infotrieve]
20. Brennan KA, Olson DM, Symonds ME. Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring. Proc Nutr Soc. 2006; 65: 116–124.[CrossRef][Medline] [Order article via Infotrieve]
21. Gopalakrishnan GS, Gardner DS, Dandrea J, Langley-Evans SC, Pearce S, Kurlak LO, Walker RM, Seetho IW, Keisler DH, Ramsay MM, Stephenson T, Symonds ME. Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. Br J Nutr. 2005; 94: 938–947.[CrossRef][Medline] [Order article via Infotrieve]
22. Langley-Evans SC. Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr. 2000; 51: 11–17.[CrossRef][Medline] [Order article via Infotrieve]
23. Oliver MH, Breier BH, Gluckman PD, Harding JE. Birth weight rather than maternal nutrition influences glucose tolerance, blood pressure, and IGF-I levels in sheep. Pediatr Res. 2002; 52: 516–524.[CrossRef][Medline] [Order article via Infotrieve]
24. Gopalakrishnan GS, Gardner DS, Rhind SM, Rae MT, Kyle CE, Brooks AN, Walker RM, Ramsay MM, Keisler DH, Stephenson T, Symonds ME. Programming of adult cardiovascular function after early maternal undernutrition in sheep. Am J Physiol Regul Integr Comp Physiol. 2004; 287: R12–R20.
25. Petry CJ, Ozanne SE, Wang CL, Hales CN. Early protein restriction and obesity independently induce hypertension in 1-year-old rats. Clin Sci (Lond). 1997; 93: 147–152.[Medline] [Order article via Infotrieve]
26. Falkner B, Hulman S, Kushner H. Birth weight versus childhood growth as determinants of adult blood pressure. Hypertension. 1998; 31: 145–150.
27. Neitzke U, Harder T, Schellong K, Melchior K, Ziska T, Rodekamp E, Dudenhausen JW, Plagemann A. Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: a critical appraisal of the experimental evidence. Placenta. 2008; 29: 246–254.[CrossRef][Medline] [Order article via Infotrieve]
28. Sanders MW, Fazzi GE, Janssen GM, de Leeuw PW, Blanco CE, De Mey JG. Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring. Hypertension. 2004; 43: 1283–1289.
29. Merlet-Benichou C, Gilbert T, Muffat-Joly M, Lelievre-Pegorier M, Leroy B. Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol. 1994; 8: 175–180.[CrossRef][Medline] [Order article via Infotrieve]
30. Bassan H, Trejo LL, Kariv N, Bassan M, Berger E, Fattal A, Gozes I, Harel S. Experimental intrauterine growth retardation alters renal development. Pediatr Nephrol. 2000; 15: 192–195.[CrossRef][Medline] [Order article via Infotrieve]
31. Briscoe TA, Rehn AE, Dieni S, Duncan JR, Wlodek ME, Owens JA, Rees SM. Cardiovascular and renal disease in the adolescent guinea pig after chronic placental insufficiency. Am J Obstet Gynecol. 2004; 191: 847–855.[CrossRef][Medline] [Order article via Infotrieve]
32. Zohdi V, Moritz KM, Bubb KJ, Cock ML, Wreford N, Harding R, Black MJ. Nephrogenesis and the renal renin-angiotensin system in fetal sheep: effects of intrauterine growth restriction during late gestation. Am J Physiol Regul Integr Comp Physiol. 2007; 293: R1267–R1273.
33. Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol. 2005; 288: R127–R133.
34. Koukkou E, Ghosh P, Lowy C, Poston L. Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular dysfunction. Circulation. 1998; 98: 2899–2904.
35. Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EH, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51: 383–392.
36. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007; 132: 2087–2102.[CrossRef][Medline] [Order article via Infotrieve]
37. Brawley L, Itoh S, Torrens C, Barker A, Bertram C, Poston L, Hanson M. Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring. Pediatr Res. 2003; 54: 83–90.[CrossRef][Medline] [Order article via Infotrieve]
38. Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D, Dominiczak AF, Hanson MA, Poston L. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension. 2003; 41: 168–175.
39. Pham TD, MacLennan NK, Chiu CT, Laksana GS, Hsu JL, Lane RH. Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003; 285: R962–R970.
40. Douglas-Denton RN, McNamara BJ, Hoy WE, Hughson MD, Bertram JF. Does nephron number matter in the development of kidney disease? Ethn Dis. 2006; 16: S2–40–45.
41. Fowden AL, Forhead AJ. Endocrine mechanisms of intrauterine programming. Reproduction. 2004; 127: 515–526.
42. Langley-Evans SC. Intrauterine programming of hypertension by glucocorticoids. Life Sci. 1997; 60: 1213–1221.[CrossRef][Medline] [Order article via Infotrieve]
43. Ortiz LA, Quan A, Zarzar F, Weinberg A, Baum M. Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension. 2003; 41: 328–334.
44. Manikkam M, Crespi EJ, Doop DD, Herkimer C, Lee JS, Yu S, Brown MB, Foster DL, Padmanabhan V. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology. 2004; 145: 790–798.
45. Crespi EJ, Steckler TL, Mohankumar PS, Padmanabhan V. Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep. J Physiol. 2006; 572: 119–130.
46. King AJ, Olivier NB, Mohankumar PS, Lee JS, Padmanabhan V, Fink GD. Hypertension caused by prenatal testosterone excess in female sheep. Am J Physiol Endocrinol Metab. 2007; 292: E1837–E1841.
47. Woods LL, Ingelfinger JR, Rasch R. Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol. 2005; 289: R1131–R1136.
48. Anderson CM, Lopez F, Zimmer A, Benoit JN. Placental insufficiency leads to developmental hypertension and mesenteric artery dysfunction in two generations of Sprague-Dawley rat offspring. Biol Reprod. 2006; 74: 538–544.
49. Ojeda NB, Grigore D, Yanes LL, Iliescu R, Robertson EB, Zhang H, Alexander BT. Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R758–R763.
50. Ojeda NB, Grigore D, Robertson EB, Alexander BT. Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring. Hypertension. 2007; 50: 679–685.
51. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart disease and stroke statistics–2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007; 115: e69–e171.
52. Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001; 37: 1199–1208.
53. Hinojosa-Laborde C, Craig T, Zheng W, Ji H, Haywood JR, Sandberg K. Ovariectomy augments hypertension in aging female Dahl salt-sensitive rats. Hypertension. 2004; 44: 405–409.
54. Chappell MC, Yamaleyeva LM, Westwood BM. Estrogen and salt sensitivity in the female mRen(2).Lewis rat. Am J Physiol Regul Integr Comp Physiol. 2006; 291: R1557–R1563.
55. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension. 1998; 31: 435–439.
56. Martin DS, Biltoft S, Redetzke R, Vogel E. Castration reduces blood pressure and autonomic venous tone in male spontaneously hypertensive rats. J Hypertens. 2005; 23: 2229–2236.[Medline] [Order article via Infotrieve]
57. Teixeira CV, Silandre D, de Souza Santos AM, Delalande C, Sampaio FJ, Carreau S, da Fonte Ramos C. Effects of maternal undernutrition during lactation on aromatase, estrogen, and androgen receptors expression in rat testis at weaning. J Endocrinol. 2007; 192: 301–311.
58. Allvin K, Ankarberg-Lindgren C, Fors H, Dahlgren J. Elevated serum levels of estradiol, dihydrotestosterone and inhibin B in adult males born small for gestational age. J Clin Endocrinol Metab. 2008; 93: 1464–1469.
59. Cicognani A, Alessandroni R, Pasini A, Pirazzoli P, Cassio A, Barbieri E, Cacciari E. Low birth weight for gestational age and subsequent male gonadal function. J Pediatr. 2002; 141: 376–379.[CrossRef][Medline] [Order article via Infotrieve]
60. Jensen RB, Vielwerth S, Larsen T, Greisen G, Veldhuis J, Juul A. Pituitary-gonadal function in adolescent males born appropriate or small for gestational age with or without intrauterine growth restriction. J Clin Endocrinol Metab. 2007; 92: 1353–1357.
61. Zambrano E, Rodriguez-Gonzalez GL, Guzman C, Garcia-Becerra R, Boeck L, Diaz L, Menjivar M, Larrea F, Nathanielsz PW. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development. J Physiol. 2005; 563: 275–284.
62. Leonhardt M, Lesage J, Croix D, Dutriez-Casteloot I, Beauvillain JC, Dupouy JP. Effects of perinatal maternal food restriction on pituitary-gonadal axis and plasma leptin level in rat pup at birth and weaning and on timing of puberty. Biol Reprod. 2003; 68: 390–400.
63. Da Silva P, Aitken RP, Rhind SM, Racey PA, Wallace JM. Influence of placentally mediated fetal growth restriction on the onset of puberty in male and female lambs. Reproduction. 2001; 122: 375–383.[Abstract]
64. Rae MT, Kyle CE, Miller DW, Hammond AJ, Brooks AN, Rhind SM. The effects of undernutrition, in utero, on reproductive function in adult male and female sheep. Anim Reprod Sci. 2002; 72: 63–71.[CrossRef][Medline] [Order article via Infotrieve]
65. van Weissenbruch MM, Engelbregt MJ, Veening MA, Delemarre-van de Waal HA. Fetal nutrition and timing of puberty. Endocr Dev. 2005; 8: 15–33.[Medline] [Order article via Infotrieve]
66. Guzman C, Cabrera R, Cardenas M, Larrea F, Nathanielsz PW, Zambrano E. Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny. J Physiol. 2006; 572: 97–108.
67. Hall JE, Brands MW, Henegar JR. Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney. J Am Soc Nephrol. 1999; 10 (suppl 12): S258–S265.[CrossRef][Medline] [Order article via Infotrieve]
68. Manning J, Vehaskari VM. Low birth weight-associated adult hypertension in the rat. Pediatr Nephrol. 2001; 16: 417–422.[CrossRef][Medline] [Order article via Infotrieve]
69. Langley-Evans SC, Jackson AA. Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comp Biochem Physiol A Physiol. 1995; 110: 223–228.[Medline] [Order article via Infotrieve]
70. Sahajpal V, Ashton N. Renal function and angiotensin AT1 receptor expression in young rats following intrauterine exposure to a maternal low-protein diet. Clin Sci (Lond). 2003; 104: 607–614.[Medline] [Order article via Infotrieve]
71. Ceravolo GS, Franco MC, Carneiro-Ramos MS, Barreto-Chaves ML, Tostes RC, Nigro D, Fortes ZB, Carvalho MH. Enalapril and losartan restored blood pressure and vascular reactivity in intrauterine undernourished rats. Life Sci. 2007; 80: 782–787.[CrossRef][Medline] [Order article via Infotrieve]
72. Ruster M, Sommer M, Stein G, Bauer K, Walter B, Wolf G, Bauer R. Renal angiotensin receptor type 1 and 2 upregulation in intrauterine growth restriction of newborn piglets. Cells Tissues Organs. 2006; 182: 106–114.[CrossRef][Medline] [Order article via Infotrieve]
73. Pladys P, Lahaie I, Cambonie G, Thibault G, Le NL, Abran D, Nuyt AM. Role of brain and peripheral angiotensin II in hypertension and altered arterial baroreflex programmed during fetal life in rat. Pediatr Res. 2004; 55: 1042–1049.[CrossRef][Medline] [Order article via Infotrieve]
74. Grigore D, Ojeda NB, Robertson EB, Dawson AS, Huffman CA, Bourassa EA, Speth RC, Brosnihan KB, Alexander BT. Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007; 293: R804–R811.
75. Song J, Kost CK Jr, Martin DS. Androgens augment renal vascular responses to ANG II in New Zealand genetically hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2006; 290: R1608–R1615.
76. Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992; 19: 456–463.
77. Gallagher PE, Li P, Lenhart JR, Chappell MC, Brosnihan KB. Estrogen regulation of angiotensin-converting enzyme mRNA. Hypertension. 1999; 33: 323–328.
78. Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, Stablein A, Beckers F, Smits JF, Daemen MJ, Vetter H, Bohm M. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation. 1998; 97: 2197–2201.
79. Ferrario CM, Chappell MC. Novel angiotensin peptides. Cell Mol Life Sci. 2004; 61: 2720–2727.[CrossRef][Medline] [Order article via Infotrieve]
80. Brosnihan KB, Neves LA, Anton L, Joyner J, Valdes G, Merrill DC. Enhanced expression of Ang-(1–7) during pregnancy. Braz J Med Biol Res. 2004; 37: 1255–1262.[Medline] [Order article via Infotrieve]
81. DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997; 77: 75–197.
82. Hall JE, Guyton AC, Brands MW. Pressure-volume regulation in hypertension. Kidney Int. 1996; 55 (suppl): S35–S41.[CrossRef]
83. I. Jzerman R, Stehouwer CD, de Geus EJ, van Weissenbruch MM, Delemarre-van de Waal HA, Boomsma DI. Low birth weight is associated with increased sympathetic activity: dependence on genetic factors. Circulation. 2003; 108: 566–571.
84. Phillips DI, Barker DJ. Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome? Diabet Med. 1997; 14: 673–677.[CrossRef][Medline] [Order article via Infotrieve]
85. Boguszewski MC, Johannsson G, Fortes LC, Sverrisdottir YB. Low birth size and final height predict high sympathetic nerve activity in adulthood. J Hypertens. 2004; 22: 1157–1163.[CrossRef][Medline] [Order article via Infotrieve]
86. Weitz G, Deckert P, Heindl S, Struck J, Perras B, Dodt C. Evidence for lower sympathetic nerve activity in young adults with low birth weight. J Hypertens. 2003; 21: 943–950.[CrossRef][Medline] [Order article via Infotrieve]
87. Petry CJ, Dorling MW, Wang CL, Pawlak DB, Ozanne SE. Catecholamine levels and receptor expression in low protein rat offspring. Diabet Med. 2000; 17: 848–853.[CrossRef][Medline] [Order article via Infotrieve]
88. Hiraoka T, Kudo T, Kishimoto Y. Catecholamines in experimentally growth-retarded rat fetus. Asia Oceania J Obstet Gynaecol. 1991; 17: 341–348.[Medline] [Order article via Infotrieve]
89. Jones CT, Robinson JS. Studies on experimental growth retardation in sheep. Plasma catecholamines in fetuses with small placenta. J Dev Physiol. 1983; 5: 77–87.[Medline] [Order article via Infotrieve]
90. Alexander BT, Hendon AE, Ferril G, Dwyer TM. Renal denervation abolishes hypertension in low-birth-weight offspring from pregnant rats with reduced uterine perfusion. Hypertension. 2005; 45: 754–758.
91. Dampney RA, Horiuchi J, Killinger S, Sheriff MJ, Tan PS, McDowall LM. Long-term regulation of arterial blood pressure by hypothalamic nuclei: some critical questions. Clin Exp Pharmacol Physiol. 2005; 32: 419–425.[CrossRef][Medline] [Order article via Infotrieve]
92. Wilcox CS. Reactive oxygen species: roles in blood pressure and kidney function. Curr Hypertens Rep. 2002; 4: 160–166.[Medline] [Order article via Infotrieve]
93. Touyz RM, Schiffrin EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol. 2004; 122: 339–352.[CrossRef][Medline] [Order article via Infotrieve]
94. Franco MC, Kawamoto EM, Gorjao R, Rastelli VM, Curi R, Scavone C, Sawaya AL, Fortes ZB, Sesso R. Biomarkers of oxidative stress and antioxidant status in children born small for gestational age: evidence of lipid peroxidation. Pediatr Res. 2007; 62: 204–208.[CrossRef][Medline] [Order article via Infotrieve]
95. Stewart T, Jung FF, Manning J, Vehaskari VM. Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension. Kidney Int. 2005; 68: 2180–2188.[CrossRef][Medline] [Order article via Infotrieve]
96. Cambonie G, Comte B, Yzydorczyk C, Ntimbane T, Germain N, Le NL, Pladys P, Gauthier C, Lahaie I, Abran D, Lavoie JC, Nuyt AM. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R1236–R1245.
97. Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S, Welch WJ, Wilcox CS. Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression. Am J Physiol Regul Integr Comp Physiol. 2003; 285: R117–R124.
98. Bagby SP. Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J Nutr. 2007; 137: 1066–1072.
99. Woods LL. Neonatal uninephrectomy causes hypertension in adult rats. Am J Physiol. 1999; 276: R974–R978.[Medline] [Order article via Infotrieve]
100. Armitage JA, Lakasing L, Taylor PD, Balachandran AA, Jensen RI, Dekou V, Ashton N, Nyengaard JR, Poston L. Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy. J Physiol. 2005; 565: 171–184.
101. Guyton AC, Coleman TG, Cowley AV Jr, Scheel KW, Manning RD Jr, Norman RA Jr. Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med. 1972; 52: 584–594.[CrossRef][Medline] [Order article via Infotrieve]
102. Hoy WE, Rees M, Kile E, Mathews JD, Wang Z. A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int. 1999; 56: 1072–1077.[CrossRef][Medline] [Order article via Infotrieve]
103. Fan ZJ, Lackland DT, Lipsitz SR, Nicholas JS. The association of low birthweight and chronic renal failure among Medicaid young adults with diabetes and/or hypertension. Public Health Rep. 2006; 121: 239–244.[Medline] [Order article via Infotrieve]
104. Li S, Chen SC, Shlipak M, Bakris G, McCullough PA, Sowers J, Stevens L, Jurkovitz C, McFarlane S, Norris K, Vassalotti J, Klag MJ, Brown WW, Narva A, Calhoun D, Johnson B, Obialo C, Whaley-Connell A, Becker B, Collins AJ. Low birth weight is associated with chronic kidney disease only in men. Kidney Int. 2008; 73: 637–642.[CrossRef][Medline] [Order article via Infotrieve]
105. Nwagwu MO, Cook A, Langley-Evans SC. Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero. Br J Nutr. 2000; 83: 79–85.[Medline] [Order article via Infotrieve]
106. Regina S, Lucas R, Miraglia SM, Zaladek Gil F, Machado Coimbra T. Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis. 2001; 37: 467–476.[Medline] [Order article via Infotrieve]
107. Gil FZ, Lucas SR, Gomes GN, Cavanal Mde F, Coimbra TM. Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats. Pediatr Res. 2005; 57: 724–731.[CrossRef][Medline] [Order article via Infotrieve]
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