Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-20T01:51:48.528Z Has data issue: false hasContentIssue false
  • English
  • Français

Prenatal programming of angiotensin II type 2 receptor expression in the rat

Published online by Cambridge University Press:  09 March 2007

Sarah McMullen ,
David S. Gardner  and
Simon C. Langley-Evans
Sarah McMullen
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, Leics., UK
David S. Gardner
Affiliation:
Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG7 2UH, UK
Simon C. Langley-Evans*
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, Leics., UK
*
*Corresponding author: Dr Simon Langley-Evans, fax +44 115 951 6122, email Simon.Langley-Evans@nottingham.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension. Epidemiological studies demonstrating relationships between low birth weight and later CVD are supported by animal experiments indicating that manipulations of the maternal diet in pregnancy exert programming effects upon blood pressure control. Pregnant female Wistar rats were fed a control diet (n 13) or a low-protein diet (n 12) throughout pregnancy. At delivery all animals were fed the same standard laboratory chow diet. Analysis of nephron number in kidneys obtained from 4-week-old offspring showed that this was significantly (P<0·05) reduced in animals exposed to maternal protein restriction. At this age rats exposed to low-protein diets in utero had systolic blood pressures that were significantly greater than those of control animals (+23 mmHg, P<0·05). Administration of ascending doses of angiotensin II (1–40 ng/kg body weight intravenously) to 10-week-old anaesthetised female rats showed that the pressor response to the peptide was greater and more prolonged in animals exposed to low-protein diets in utero. Renal expression of mRNA for the angiotensin II type 1A receptor was similar in the two groups of rats, but low-protein-exposed animals had significantly lower renal expression of the type 2 receptor (P=0·023). These results suggest that maternal nutritional status programmes expression of the renal angiotensin II type 2 receptor. This may play a key role in the impairment of renal development and the elevation of blood pressure noted in rats exposed to intra-uterine protein restriction.

Keywords

Angiotensin II receptorsFetal programmingLow-protein diet
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 1 , January 2004 , pp. 133 - 140
Copyright
Copyright © The Nutrition Society 2004

References

Allen, AM, Zhuo, JL & Mendelsohn, FAO (2000) Localization and function of angiotensin angiotensin (1) receptors. Am J Hypertens 13, 31S–38S.CrossRefGoogle Scholar
Barker, DJP (1995) The fetal and infant origins of disease. Eur J Clin Invest 25, 457–463.CrossRefGoogle ScholarPubMed
Beach, RS, Gershwin, ME & Hurley, LS (1982) Gestational zinc deprivation in mice: persistence of immunodeficiency for three generations. Science 218, 469–471.Google Scholar
Bertram, C, Trowern, AR, Copin, N, Jackson, AA & Whorwood, CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11 beta-hydroxysteroid dehydrogenase: Potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142, 2841–2853.Google Scholar
Bunag, RD (1991) Measurement of blood pressure in rats. In Handbook of Hypertension. 14: Blood Pressure Measurement, pp. 351–370[O'Brien, E, O'Malley, KO, editors]. New York: Elsevier.Google Scholar
Campbell, DM, Hall, MH, Barker, DJP, Cross, J, Shiell, AW & Godfrey, KM (1996) Diet in pregnancy and the offsprings blood pressure 40 years later. Br J Obstet Gynaecol 103, 273–280.CrossRefGoogle ScholarPubMed
Curhan, GC, Chertow, GM & Willett, WC (1996) Birth weight and adult hypertension and obesity in women. Circulation 94, 1310–1315.Google Scholar
Dahri, S, Snoeck, A, Reusens-Billen, B, Remacle, C & Hoet, JJ (1991) Islet function in offspring of mothers on low protein diet during gestation. Diabetes 40, 115–120.Google Scholar
Edwards, CRW, Benediktsson, R, Lindsay, RS & Seckl, JR (1993) Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension. Lancet 341, 355–357.CrossRefGoogle ScholarPubMed
Fall, CHD, Vijayakumar, M, Barker, DJP, Osmond, C & Duggleby, S (1995) Weight in infancy and prevalence of coronary heart disease in adult life. Br Med J 310, 17–19.Google Scholar
Forsen, T, Eriksson, JG, Tuomilehto, J, Osmond, C & Barker, DJP (1999) Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study. Br Med J 319, 1403–1407.CrossRefGoogle ScholarPubMed
Gardner, DS, Jackson, AA & Langley-Evans, SC (1997) Maintenance of maternal diet-induced hypertension in the rat is dependent upon glucocorticoids. Hypertension 30, 1525–1530.CrossRefGoogle ScholarPubMed
Goto, M, Mukoyama, M & Suga, S (1997) Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells. Hypertension 30, 358–362.CrossRefGoogle ScholarPubMed
Goto, et al.. 1998Google Scholar
Hales, CN, Barker, DJP, Clark, PMS, et al. (1991) Fetal and infant growth and impaired glucose-tolerance at age 64. Br Med J 303, 1019–1022.Google Scholar
Hoy, WE, Mathews, JD, McCredie, DA, et al. (1998) The multidimensional nature of renal disease: Rates and associations of albuminuria in an Australian Aboriginal community. Kidney Int 54, 1296–1304.CrossRefGoogle Scholar
Huxley, R, Neil, A & Collins, R (2002) Unravelling the fetal origins hypothesis: is there really an inverse association between birth weight and subsequent blood pressure?. Lancet 360, 659–665.CrossRefGoogle ScholarPubMed
Ichiki, T, Labosky, PA & Shiota, C (1995) Effects on blood pressure and exploratory behaviour of mice lacking angtiotensin II type-2 receptor. Nature 377, 748–750.CrossRefGoogle Scholar
Iglesias-Barreira, V, Ahn, M-T, Reussens, B, Dahri, S, Hoet, JJ & Remacle, C (1996) Pre- and postnatal low protein diet affect pancreatic islet blood flow and insulin release in adult rats. Endocrinology 137, 3797–3801.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (2001) Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc Nutr Soc 60, 505–513.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Jackson, AA (1995) Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comp Biochem Physiol 110A, 223–228.CrossRefGoogle Scholar
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 a) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fertil 106, 307–312.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 b) Evidence of programming of the hypothalamic–pituitary–adrenal axis by maternal protein restriction during pregnancy. J Nutr 126, 1578–1585.CrossRefGoogle Scholar
Langley-Evans, SC & Nwagwu, M (1998) Impaired growth and increased activities of glucocorticoid sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets. Life Sci 63, 605–615.Google Scholar
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1994) In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr 13, 319–324.Google Scholar
Langley-Evans, SC, Welham, SJM & Jackson, AA (1999) Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 64, 965–974.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM, Sherman, RC & Jackson, AA (1996 c) Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clin Sci 91, 607–615.CrossRefGoogle ScholarPubMed
Law, CM, de Swiet, M & Osmond, C (1993) Initiation of hypertension in utero and its amplification throughout life. Br Med J 306, 24–27.Google Scholar
Manalich, R, Reye, 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.Google Scholar
Marchand, MC & Langley-Evans, SC (2001) Intrauterine programming of nephron number: the fetal flaw revisited. J Nephrol 14, 327–331.Google ScholarPubMed
Martyn, CN, Barker, DJP, Jespersen, S, Greenwald, S, Osmond, C & Berry, C (1995) Growth in utero, adult blood pressure and arterial compliance. Br Heart J 73, 116–121.CrossRefGoogle ScholarPubMed
Mehta, G, Roach, HI & Langley-Evans, SC (2002) Intrauterine exposure to a maternal low protein diet reduces adult bone mass and alters growth plate morphology. Calcif Tiss Int 79, 493–498.Google Scholar
Miyata, N, Park, F, Li, XF & Cowley, AW (1999) Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney. Am J Physiol 277, F437–F446.Google ScholarPubMed
Oliverio, MI, Best, CF, Kim, HS, Arendshorst, WJ, Smithies, O & Coffman, TM (1997) Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation. Am J Physiol. 272, F299–F304.Google Scholar
Phillips, DIW, Barker, DJP, Hales, CN, Hirst, S & Osmond, C (1994) Thinness at birth and insulin resistance in adult life. Diabetologia 37, 150–154.CrossRefGoogle ScholarPubMed
Saglikes, Y, Massry, SG & Iseki, K (1985) Effect of phosphate depletion on blood pressure and vascular reactivity to norepinephrine and angiotensin II in the rat. Am J Physiol 248, F93–F99.Google ScholarPubMed
Sahajpal, V & Ashton, N (2003) Renal function and AT1 receptor expression in young rats following intrauterine exposure to a maternal low protein diet. Clin Sci 104, 607–614.CrossRefGoogle ScholarPubMed
Sayer, AA, Dunn, RL, Langley-Evans, SC & Cooper, C (2001) Intrauterine exposure to a maternal low protein diet shortens lifespan in rats. Gerontology 47, 9–14.Google Scholar
Sherman, RC & Langley-Evans, SC (1998) Early administration of angiotensin converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low protein diet in the rat. Clin Sci 94, 373–381.CrossRefGoogle ScholarPubMed
Sherman, RC & Langley-Evans, SC (2000) Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure, in the rat. Clin Sci 98, 269–275.CrossRefGoogle ScholarPubMed
Sheuer, DA & Perrone, MH (1993) Angiotensin type 2 receptors mediate depressor phase of biphasic response to angiotensin. Am J Physiol 264, R917–R923.Google Scholar
Siragy, HM (2002) Angiotensin receptor blockers: how important is selectivity?. Am J Hypertens 15, 1006–1014.CrossRefGoogle ScholarPubMed
Siragy, HM & Carey, RM (1997) The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 100, 264–269.CrossRefGoogle ScholarPubMed
Vehaskari, VM, Aviles, DH & Manning, J (2001) Prenatal programming of adult hypertension in the rat. Kidney Int 59, 238–245.CrossRefGoogle ScholarPubMed
Weber, KT, Sun, Y & Guarda, E (1994) Structural remodelling in hypertensive heart disease and the role of hormones. Hypertension 23, 869–877.CrossRefGoogle ScholarPubMed
Welham, SJM, Wade, A & Woolf, AS (2002) Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int 61, 1231–1242.CrossRefGoogle ScholarPubMed