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Licensed Unlicensed Requires Authentication Published by De Gruyter December 17, 2015

Genetic low nephron number hypertension is associated with altered expression of key components of the renin-angiotensin system during nephrogenesis

  • Anne Lena Faensen EMAIL logo , Markus Wehland von Trebra , Florian Freese , Reinhold Kreutz , Christian Bamberg , Larry Hinkson and Lars Rothermund



This study investigates key components of the renin-angiotensin system (RAS) which play a central role in nephrogenesis and possibly in fetal programming of arterial hypertension in adult life.


We compared a genetic rat model with inborn nephron deficit, the Munich Wistar Fromter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postnatal day 7 (D7).


At E19 renal mRNA of angiotensin II type 1a (AT1a) (–50%, P<0.05) and type 1b (AT1b) (–55%, P<0.05) receptors were significantly decreased and renal mRNA expression of angiotensin II type 2(AT2)receptor was fivefold increased in MWF (n=8) as compared to Wistar rats (n=8). At D7 renal mRNA expression of AT1a (–42%, P<0.05) remained lower in MWF (n=8) as compared to Wistar (n=7). Renal mRNA expression of AT2 (–30%, P>0.05) decreased in MWF (n=8) to about the level of the Wistar control (n=6).


Altered fetal expression of key molecules of the renin-angiotensin system in MWF indicates a possible role in genetic low nephron number hypertension.

Corresponding author: Anne Lena Faensen, née Freese, Klinik für Geburtsmedizin, Charité-Universitätsmedizin, Augustenburgerplatz 1, 13353 Berlin, Germany, Tel.: +49-30-450564072, Fax: +49-30-450564901, E-mail: ; und Institut für Klinische Pharmakologie und Toxikologie, Charité-Universitätsmedizin Berlin, Berlin, Germany


[1] Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989;ii:577–80.10.1016/S0140-6736(89)90710-1Search in Google Scholar

[2] Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertension. 1988;1(4 Pt 1):335–47.10.1093/ajh/1.4.335Search in Google Scholar

[3] Manalich R, Reyes L, Herrera M, Melendi C, Fundora I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000;58:770–3.10.1046/j.1523-1755.2000.00225.xSearch in Google Scholar

[4] Rodriguez MM, Gomez A, Abitbol C, Chandar J, Montane B, Zilleruelo G. Comparative renal histomorphometry: a case study of oligonephropathy of prematurity. Pediatr Nephrol. 2005;20:945–9.10.1007/s00467-004-1800-xSearch in Google Scholar

[5] Godfrey KM, Barker DJ. Maternal nutrition in relation to fetal and placental growth. Eur J Obstet Gynecol Reprod Biol. 1995;61:15–22.10.1016/0028-2243(95)02148-LSearch in Google Scholar

[6] Langley SC, Jackson AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci. 1994;86:217–22; discussion 121.10.1042/cs0860217Search in Google Scholar PubMed

[7] 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;8:175–80.10.1007/BF00865473Search in Google Scholar PubMed

[8] Freese A, Wehland M, Freese F, Bamberg C, Kreutz R, Rothermund L. Genetic low nephron number hypertension is associated with altered expression of osteopontin and CD44 during nephrogenesis. J Perinat Med. 2013;41:295–9.10.1515/jpm-2012-0178Search in Google Scholar PubMed

[9] Yosypiv IV. Renin-angiotensin system in ureteric bud branching morphogenesis: implications for kidney disease. Pediatr Nephrol. 2014;29:609–20.10.1007/s00467-013-2616-3Search in Google Scholar PubMed

[10] Madsen K, Tinning AR, Marcussen N, Jensen BL. Postnatal development of the renal medulla; role of the renin-angiotensin system. Acta Physiol. 2013;208:41–9.10.1111/apha.12088Search in Google Scholar PubMed

[11] Norwood VF, Craig MR, Harris JM, Gomez RA. Differential expression of angiotensin II receptors during early renal morphogenesis. Am J Physiol. 1997;272(2 Pt 2):R662–8.10.1152/ajpregu.1997.272.2.R662Search in Google Scholar PubMed

[12] Wolf G. Angiotensin II and tubular development. Nephrol Dial Transplant. 2002;17(Suppl 9):48–51.10.1093/ndt/17.suppl_9.48Search in Google Scholar PubMed

[13] Chen Y, Lasaitiene D, Friberg P. The renin-angiotensin system in kidney development. Acta Physiol Scand. 2004;181:529–35.10.1111/j.1365-201X.2004.01327.xSearch in Google Scholar PubMed

[14] Guron G, Marcussen N, Nilsson A, Sundelin B, Friberg P. Postnatal time frame for renal vulnerability to enalapril in rats. J Am Soc Nephrol. 1999;10:1550–60.10.1681/ASN.V1071550Search in Google Scholar PubMed

[15] Guron G, Friberg P. An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertension. 2000;18:123–37.10.1097/00004872-200018020-00001Search in Google Scholar PubMed

[16] Fassi A, Sangalli F, Maffi R, Colombi F, Mohamed EI, Brenner BM, et al. Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit. J Am Soc Nephrol. 1998;9:1399–406.10.1681/ASN.V981399Search in Google Scholar PubMed

[17] Hackbarth H, Buttner D, Jarck D, Pothmann M, Messow C, Gartner K. Distribution of glomeruli in the renal cortex of Munich Wistar Fromter (MWF) rats. Ren Physiol. 1983;6:63–71.10.1159/000172882Search in Google Scholar PubMed

[18] Kreutz R, Kovacevic L, Schulz A, Rothermund L, Ketteler M, Paul M. Effect of high NaCl diet on spontaneous hypertension in a genetic rat model with reduced nephron number. J Hypertension. 2000;18:777–82.10.1097/00004872-200018060-00017Search in Google Scholar PubMed

[19] Rovira-Halbach G, Alt JM, Brunkhorst R, Frei U, Kuhn K, Stolte H. Single nephron hyperfiltration and proteinuria in a newly selected rat strain with superficial glomeruli. Ren Physiol. 1986;9:317–25.10.1159/000173097Search in Google Scholar PubMed

[20] Rothermund L, Nierhaus M, Fialkowski O, Freese F, Ibscher R, Mieschel S, et al. Genetic low nephron number hypertension is associated with dysregulation of the hepatic and renal insulin-like growth factor system during nephrogenesis. J Hypertension. 2006;24:1857–64.10.1097/01.hjh.0000242411.50536.b9Search in Google Scholar PubMed

[21] Woods LL, Rasch R. Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats. Am J Physiol. 1998;275(5 Pt 2):R1593–9.10.1152/ajpregu.1998.275.5.R1593Search in Google Scholar PubMed

[22] Hilgers KF, Norwood VF, Gomez RA. Angiotensin’s role in renal development. Semin Nephrol. 1997;17(5):492–501.Search in Google Scholar

[23] Norwood VF, Garmey M, Wolford J, Carey RM, Gomez RA. Novel expression and regulation of the renin-angiotensin system in metanephric organ culture. Am J Physiol Regul Integr Comp Physiol. 2000;279:R522–30.10.1152/ajpregu.2000.279.2.R522Search in Google Scholar PubMed

[24] 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;49:460–7.10.1203/00006450-200104000-00005Search in Google Scholar PubMed

[25] Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA. 1996;93:156–60.10.1073/pnas.93.1.156Search in Google Scholar PubMed PubMed Central

The authors stated that there are no conflicts of interest regarding the publication of this article.

Article note:

Supported by the Deutsche Forschungsgemeinschaft (DFG,GrantRO 2124/2-1 and RO 2124/2-2).

Received: 2015-6-2
Accepted: 2015-11-2
Published Online: 2015-12-17
Published in Print: 2016-8-1

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