Abstract
Low birth weight (LBW) due to intrauterine growth restriction (IUGR) in humans is associated with increased blood pressure (BP) in adulthood. In Western countries, IUGR is based on uteroplacental dysfunction. We used an animal model of uteroplacental dysfunction to evaluate this correlation. We hypothesize that IUGR increases baseline BP and alters the BP response to acute stress, which may explain BP differences in previous studies using stressful methods to obtain BP. IUGR was induced by bilateral uterine artery ligation in pregnant Wistar rats according to a modified method of Wigglesworth. BP was measured in the offspring using telemetry, allowing for unstressed measurements in conscious animals. Cardiovascular data were obtained at the age of 12 wk during baseline and acute olfactory stress induced by an ammonia gauze. Rats born after IUGR had a lower birth weight versus controls and did not completely catch up in weight. At baseline, systolic BP (SBP), mean arterial pressure (MAP), and pulse pressure (PP) were elevated in IUGR rats versus controls, by 8, 6, and 5 mm Hg, respectively. There was a strong negative correlation between birth weight and SBP and between birth weight and PP. During acute stress, there was a tendency to reach a higher peak in SBP and to need a longer period to recover in IUGR animals. We conclude that IUGR is associated with increased baseline BP.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BP:
-
blood pressure
- CTRL:
-
control
- DBP:
-
diastolic blood pressure
- HR:
-
heart rate
- IUGR:
-
intrauterine growth restriction
- LBW:
-
low birth weight
- MAP:
-
mean arterial pressure
- PP:
-
pulse pressure
- SBP:
-
systolic blood pressure
- SLA:
-
spontaneous locomotor action
References
Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD 1991 Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303: 1019–1022
Barker DJ 1995 Fetal origins of coronary heart disease. BMJ 311: 171–174
Godfrey KM, Barker DJ 2000 Fetal nutrition and adult disease. Am J Clin Nutr 71: 1344S–1352S
Barker DJ 2001 The malnourished baby and infant. Br Med Bull 60: 69–88
Huxley RR, Shiell AW, Law CM 2000 The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18: 815–831
Beech DJ, Sibbons PD, Howard CV, van Velzen D 2000 Renal developmental delay expressed by reduced glomerular number and its association with growth retardation in victims of sudden infant death syndrome and in "normal" infants. Pediatr Dev Pathol 3: 450–454
Hinchliffe SA, Lynch MR, Sargent PH, Howard CV, van Velzen D 1992 The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol 99: 296–301
Merlet-Benichou C, Gilbert T, Vilar J, Moreau E, Freund N, Lelievre-Pegorier M 1999 Nephron number: variability is the rule. Causes and consequences. Lab Invest 79: 515–527
Zidar N, Cor A, Premru Srsen T, Stajer D 1998 Is there an association between glomerular density and birth weight in healthy humans. Nephron 80: 97–98
Manalich R, Reyes L, Herrera M, Melendi C, Fundora I 2000 Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58: 770–773
Merlet-Benichou C, Vilar J, Lelievre-Pegorier M, Moreau E, Gilbert T 1997 Fetal nephron mass: its control and deficit. Adv Nephrol Necker Hosp 26: 19–45
Hughson M, Farris AB 3rd, Douglas-Denton R, Hoy WE, Bertram JF 2003 Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 63: 2113–2122
Pham TD, MacLennan NK, Chiu CT, Laksana GS, Hsu JL, Lane RH 2003 Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol 285: R962–R970
Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM 1981 Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 241: F85–F93
Brenner BM, Lawler EV, Mackenzie HS 1996 The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int 49: 1774–1777
Garrett PJ, Bass PS, Sandeman DD 1994 Barker, Brenner, and babies–early environment and renal disease in adulthood. J Pathol 173: 299–300
Brenner BM, Garcia DL, Anderson S 1988 Glomeruli and blood pressure. Less of one, more the other?. Am J Hypertens 1: 335–347
Keller G, Zimmer G, Mall G, Ritz E, Amann K 2003 Nephron number in patients with primary hypertension. N Engl J Med 348: 101–108
Holemans K, Aerts L, Van Assche FA 2003 Fetal growth restriction and consequences for the offspring in animal models. J Soc Gynecol Invest 10: 392–399
Kramer K, Kinter LB 2003 Evaluation and applications of radiotelemetry in small laboratory animals. Physiol Genomics 13: 197–205
Cherney A, Edgell H, Krukoff TL 2003 NO mediates effects of estrogen on central regulation of blood pressure in restrained, ovariectomized rats. Am J Physiol Regul Integr Comp Physiol 285: R842–R849
Tonkiss J, Trzcinska M, Galler JR, Ruiz-Opazo N, Herrera VL 1998 Prenatal malnutrition-induced changes in blood pressure: dissociation of stress and nonstress responses using radiotelemetry. Hypertension 32: 108–114
Jansson T, Lambert GW 1999 Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age. J Hypertens 17: 1239–1248
Henriksen T, Clausen T 2002 The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet Gynecol Scand 81: 112–114
Campbell T, Lin S, DeVries C, Lambert K 2003 Coping strategies in male and female rats exposed to multiple stressors. Physiol Behav 78: 495–504
Pan TM, Shimoda K, Cai Y, Kiuchi Y, Nakama K, Akimoto T, Nagashima Y, Kai M, Ohira M, Saegusa J, et al. 1995 Deodorization of laboratory animal facilities by ozone. Exp Anim 44: 255–259
Wigglesworth JS 1964 Experimental growth retardation in the foetal rat. J Pathol Bacteriol 88: 1–13
Leon LR, Walker LD, DuBose DA, Stephenson LA 2004 Biotelemetry transmitter implantation in rodents: impact on growth and circadian rhythms. Am J Physiol Regul Integr Comp Physiol 286: R967–R974
Brockway BP, Mills PA, Azar SH 1991 A new method for continuous chronic measurement and recording of blood pressure, heart rate and activity in the rat via radio-telemetry. Clin Exp Hypertens A 13: 885–895
Milligan SR, Sales GD, Khirnykh K 1993 Sound levels in rooms housing laboratory animals: an uncontrolled daily variable. Physiol Behav 53: 1067–1076
Davy KP, Hall JE 2004 Obesity and hypertension: two epidemics or one?. Am J Physiol Regul Integr Comp Physiol 286: R803–R813
Huxley R, Neil A, Collins R 2002 Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure?. Lancet 360: 659–665
Franklin SS, Khan SA, Wong ND, Larson MG, Levy D 1999 Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation 100: 354–360
Cheung YF, Wong KY, Lam BC, Tsoi NS 2004 Relation of arterial stiffness with gestational age and birth weight. Arch Dis Child 89: 217–221
Lemmer B, Mattes A, Bohm M, Ganten D 1993 Circadian blood pressure variation in transgenic hypertensive rats. Hypertension 22: 97–101
Ortiz LA, Quan A, Weinberg A, Baum M 2001 Effect of prenatal dexamethasone on rat renal development. Kidney Int 59: 1663–1669
Podjarny E, Baylis C, Losonczy G 1999 Animal models of preeclampsia. Semin Perinatol 23: 2–13
Langley-Evans SC, Welham SJ, Jackson AA 1999 Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 64: 965–974
Woodall SM, Johnston BM, Breier BH, Gluckman PD 1996 Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatr Res 40: 438–443
Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP 2000 Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127: 4195–4202
Persson E, Jansson T 1992 Low birth weight is associated with elevated adult blood pressure in the chronically catheterized guinea-pig. Acta Physiol Scand 145: 195–196
Poore KR, Forhead AJ, Gardner DS, Giussani DA, Fowden AL 2002 The effects of birth weight on basal cardiovascular function in pigs at 3 months of age. J Physiol 539: 969–978
Dodic M, Abouantoun T, O'Connor A, Wintour EM, Moritz KM 2002 Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension 40: 729–734
Schreuder MF, Nyengaard JR, Fodor M, Van Wijk JA, Delemarre-van de Waal HA 2005 Glomerular number and function are influenced by spontaneous and induced low birth weight in rats. J Am Soc Nephrol 16: 2913–2919
Acknowledgements
We would like to thank dr. K. Kramer for his expert advise on the telemetry system and Michiel Oosterveld for his helpful suggestions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schreuder, M., Fodor, M., van Wijk, J. et al. Association of Birth Weight with Cardiovascular Parameters in Adult Rats During Baseline and Stressed Conditions. Pediatr Res 59, 126–130 (2006). https://doi.org/10.1203/01.pdr.0000190576.08501.df
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.pdr.0000190576.08501.df
This article is cited by
-
Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR
Pediatric Research (2021)
-
Bone growth and sexual dimorphism at birth in intrauterine-growth-retarded rats
Anatomical Science International (2011)


