Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring. It was observed that the offspring from dams submitted to high-sodium intake during pregnancy present disturbances in renal development and in blood pressure. These alterations were associated with lower plasma levels of angiotensin II (AII) and changes in renal AII receptor I (AT1) and mitogen-activated protein kinase (MAPK) expressions during post natal kidney development. Clinical and experimental evidence show that the renin-angiotensin system (RAS) participates in renal development. Many effects of AII are mediated through MAPK pathways. Extracellular signal-regulated protein kinases (ERKs) play a pivotal role in cellular proliferation and differentiation. In conclusion, high-sodium intake during pregnancy and lactation can provoke disturbances in renal development in offspring leading to functional and structural alterations that persist in adult life. These changes can be related at least in part with the decrease in RAS activity considering that this system has an important role in renal development. 1. Introduction The risk of hypertension, renal, and cardiovascular disease are in part determined before birth by intrauterine factors. Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring [1, 2]. The nephrogenesis in rats begins on embryonic day 12 and is completed at between 10 and 15 days after birth [3, 4]. Clinical and experimental evidence show that the renin-angiotensinn system (RAS) participates in renal development [5–11]. In the rat kidney, angiotensinogen expression is higher during the late gestation and newborn period whilst renin mRNA is detected from embryonic day 17 and is higher on embryonic day 20 and in newborns compared to adults [7, 8]. Renal AII content is several fold higher in newborn rats and mice than in their adult counterparts. The AII receptors are also expressed to a greater degree in newborn rats [9]. The mRNA for the type 1 AII receptor (AT1) has been detected in the renal glomeruli of newborn rats during cellular proliferation and differentiation [10]. Increase in fibronectin, -SM-actin ( -smooth muscle actin), PCNA (proliferating cell nuclear antigen) and p-ERK (extracellular signal-regulated protein kinase) expressions were observed in the renal cortex of 1- and 7-day-old rats, followed by a decrease during renal development [12].
References
[1]
D. J. P. Barker, S. P. Bagby, and M. A. Hanson, “Mechanisms of disease: in utero programming in the pathogenesis of hypertension,” Nature Clinical Practice Nephrology, vol. 2, no. 12, pp. 700–707, 2006.
[2]
V. M. Vehaskari, D. H. Aviles, and J. Manning, “Prenatal programming of adult hypertension in the rat,” Kidney International, vol. 59, no. 1, pp. 238–245, 2001.
[3]
S. K. Nigam, A. C. Aperia, and B. M. Brenner, “Development and maturation of the kidney,” in Dans: The Kidney: Physiology and Pathology, B. M. Brenner and F.C. Rector, Eds., pp. 72–98, WB Saunders, Philadelphia, Pa, USA, 5th edition, 1996.
[4]
W. Reeves, J. P. Caulfield, and M. G. Farquhar, “Differentiation of epithelial foot processes and filtration slits. Sequential appearance of occluding junctions, epithelial polyanion, and slit membranes in developing glomeruli,” Laboratory Investigation, vol. 39, no. 2, pp. 90–100, 1978.
[5]
A. S. Woolf and P. J. D. Winyard, “Advances in the cell biology and genetics of human kidney malformations,” Journal of the American Society of Nephrology, vol. 9, no. 6, pp. 1114–1125, 1998.
[6]
I. V. Yosypiv, M. Schroeder, and S. S. El-Dahr, “Angiotensin II type 1 receptor-EGF receptor cross-talk regulates ureteric bud branching morphogenesis,” Journal of the American Society of Nephrology, vol. 17, no. 4, pp. 1005–1014, 2006.
[7]
R. A. Gomez, K. R. Lynch, B. C. Sturgill et al., “Distribution of renin mRNA and its protein in the developing kidney,” American Journal of Physiology, vol. 257, no. 5, pp. F850–F858, 1989.
[8]
R. A. Gomez, A. Tufro-McReddie, A. D. Everett, and E. S. Pentz, “Ontogeny of renin and AT1 receptor in the rat,” Pediatric Nephrology, vol. 7, no. 5, pp. 635–638, 1993.
[9]
M. A. Millan, P. Carvallo, S. Izumi, S. Zemei, K. J. Catt, and G. Aguilera, “Novel sites of expression of functional angiotensin II receptors in the late gestation fetus,” Science, vol. 244, no. 4910, pp. 1340–1342, 1989.
[10]
A. Tufro-McReddie, J. K. Harrison, A. D. Everett, and R. A. Gomez, “Ontogeny of type 1 angiotensin II receptor gene expression in the rat,” Journal of Clinical Investigation, vol. 91, no. 2, pp. 530–537, 1993.
[11]
E. F. Grady, L. A. Sechi, C. A. Griffin, M. Schambelan, and J. E. Kalinyak, “Expression of AT2 receptors in the developing rat fetus,” Journal of Clinical Investigation, vol. 88, no. 3, pp. 921–933, 1991.
[12]
A. P. C. Balbi, R. S. Costa, and T. M. Coimbra, “Postnatal renal development of rats from mothers that received increased sodium intake,” Pediatric Nephrology, vol. 19, no. 11, pp. 1212–1218, 2004.
[13]
A. B. Roberts, B. K. McCune, and M. B. Sporn, “TGF-β: regulation of extracellular matrix,” Kidney International, vol. 41, no. 3, pp. 557–559, 1992.
[14]
J. P. Thiery, J. L. Duband, S. Dufour, P. Savagner, and B. A. Imhof, “Role of fibronectins in embryogenesis,” in Dans: Biology of Extracellular Matrix: Fibronectin, D. F. Mosher, Ed., pp. 181–212, Academic Press, San Diego, Calif, USA, 1989.
[15]
A. V. Carey, R. M. Carey, and R. A. Gomez, “Expression of α-smooth muscle actin in the developing kidney vasculature,” Hypertension, vol. 19, no. 2, supplement, pp. II168–II175, 1992.
[16]
K. Naruse, M. Fujieda, E. Miyazaki et al., “An immunohistochemical study of developing glomeruli in human fetal kidneys,” Kidney International, vol. 57, no. 5, pp. 1836–1846, 2000.
[17]
S. Omori, M. Hida, K. Ishikura, S. Kuramochi, and M. Awazu, “Expression of mitogen-activated protein kinase family in rat renal development,” Kidney International, vol. 58, no. 1, pp. 27–37, 2000.
[18]
O. Gribouval, M. Gonzáles, T. Neuhaus et al., “Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis,” Nature Genetics, vol. 37, no. 9, pp. 964–968, 2005.
[19]
F. Niimura, P. A. Labosky, J. Kakuchi et al., “Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation,” Journal of Clinical Investigation, vol. 96, no. 6, pp. 2947–2954, 1995.
[20]
T. Kubo, T. Ibusuki, S. Chiba, T. Kambe, and R. Fukumori, “Mitogen-activated protein kinase activity regulation role of angiotensin and endothelin systems in vascular smooth muscle cells,” European Journal of Pharmacology, vol. 411, no. 1-2, pp. 27–34, 2001.
[21]
B. M. Choi, K. H. Yoo, I. S. Bae et al., “Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney,” Pediatric Research, vol. 57, no. 1, pp. 115–123, 2005.
[22]
D. Kumar, V. Menon, W. R. Ford, A. S. Clanachan, and B. I. Jugdutt, “Effect of angiotensin II type 2 receptor blockade on mitogen activated protein kinase during myocardial ischemia-reperfusion,” Molecular and Cellular Biochemistry, vol. 258, no. 1-2, pp. 211–218, 2004.
[23]
M. Hida, S. Omori, and M. Awazu, “ERK and p38 MAP kinase are required for rat renal development,” Kidney International, vol. 61, no. 4, pp. 1252–1262, 2002.
[24]
E. C. S. Marin, A. P. C. Balbi, H. D. C. Francescato, C. G. Alves Da Silva, R. S. Costa, and T. M. Coimbra, “Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy,” Renal Failure, vol. 30, no. 5, pp. 547–555, 2008.
[25]
H. D. Cardoso, E. V. Cabral, L. D. Vieira-Filho, A. Vieyra, and A. D. O. Paix？o, “Fetal development and renal function in adult rats prenatally subjected to sodium overload,” Pediatric Nephrology, vol. 24, no. 10, pp. 1959–1965, 2009.
[26]
N. Koleganova, G. Piecha, E. Ritz et al., “Both high and low maternal salt intake in pregnancy alter kidney development in the off spring,” American Journal of Physiology, vol. 301, no. 2, pp. F344–F354, 2011.
[27]
R. J. Johnson, C. E. Alpers, A. Yoshimura et al., “Renal injury from angiotensin II-mediated hypertension,” Hypertension, vol. 19, no. 5, pp. 464–474, 1992.
[28]
Y. Chen, D. Lasaitiene, B. G. Gabrielsson et al., “Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions,” Journal of the American Society of Nephrology, vol. 15, no. 5, pp. 1232–1243, 2004.
[29]
R. P. Jankov, A. Negus, and A. K. Tanswell, “Antioxidants as therapy in the newborn: some words of caution,” Pediatric Research, vol. 50, no. 6, pp. 681–687, 2001.
[30]
A. Beauséjour, V. Houde, K. Bibeau, R. Gaudet, J. St-Louis, and M. Brochu, “Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat,” American Journal of Physiology, vol. 293, no. 4, pp. R1657–R1665, 2007.
[31]
C. Zhang, S. Z. Imam, S. F. Ali, and P. R. Mayeux, “Peroxynitrite and the regulation of Na+,K+-ATPase activity by angiotensin II in the rat proximal tubule,” Nitric Oxide, vol. 7, no. 1, pp. 30–35, 2002.
[32]
N. J. Guzman, M. Z. Fang, S. S. Tang, J. R. Ingelfinger, and L. C. Garg, “Autocrine inhibition of Na+/K+-ATPase by nitric oxide in mouse proximal tubule epithelial cells,” Journal of Clinical Investigation, vol. 95, no. 5, pp. 2083–2088, 1995.
[33]
D. G. Kang, J. W. Kim, and J. Lee, “Effects of nitric oxide synthesis inhibition on the Na,K-ATPase activity in the kidney,” Pharmacological Research, vol. 41, no. 1, pp. 123–127, 2000.
[34]
K. S. Eardley and P. Cockwell, “Macrophages and progressive tubulointerstitial disease,” Kidney International, vol. 68, no. 2, pp. 437–455, 2005.
[35]
N. Hazon, C. Parker, R. Leonard, and I. W. Henderson, “Influence of an enriched dietary sodium chloride regime during gestation and suckling and post-natally on the ontogeny of hypertension in the rat,” Journal of Hypertension, vol. 6, no. 7, pp. 517–524, 1988.
[36]
A. A. da Silva, I. L. de Noronha, I. B. de Oliveira, D. M. C. Malheiros, and J. C. Heimann, “Renin-angiotensin system function and blood pressure in adult rats after perinatal salt overload,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 13, no. 3, pp. 133–139, 2003.
[37]
K. E. Moe, “The salt intake of rat dams influences the salt intake and brain angiotensin receptors of their adult offspring,” Society of Neuroscience Abstract, vol. 13, Article ID 1169A, 1987.
[38]
R. J. Contreras, D. L. Wong, R. Henderson, K. S. Curtis, and J. C. Smith, “High dietary NaCl early in development enhances mean arterial pressure of adult rats,” Physiology and Behavior, vol. 71, no. 1-2, pp. 173–181, 2000.
[39]
R. J. Contreras, “Differences in perinatal NaCl exposure alters blood pressure levels of adult rats,” American Journal of Physiology, vol. 256, no. 1, pp. R70–R77, 1989.
[40]
J. P. Porter, S. H. King, and A. D. Honeycutt, “Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring,” American Journal of Physiology, vol. 293, no. 1, pp. R334–R342, 2007.
