gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Genetic Low Nephron Number Hypertension is Associated with Downregulation of the Hepatic Insulin-like Growth Factor System during Nephrogenesis

Angeborener Nephron-Mangel ist mit einer Downregulation des Insulin-like Growth Faktor Systems während der Nephrogenese assoziiert

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  • L. Rothermund - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)
  • R. Kreutz - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)
  • M. Nierhaus - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)
  • F. Freese - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)
  • S. Mieschel - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)
  • W. Zidek - Charité - Universitätsmedizin Berlin Campus Benjamin Franklin Berlin (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP40

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch040.shtml

Published: August 8, 2006

© 2006 Rothermund et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Objective: Low nephron number may represent a major determinant of human primary hypertension in adult life. This hypothesis is supported by a genetic rat model, i.e. the Munich-Wistar Frömter (MWF) rat, which demonstrates an inherited deficit in nephron number and the development of spontaneous hypertension. Insulin-like growth factor-I (IGF-I) and -II (IGF-II) are bound to specific insulin-like growth factor binding proteins (IGFBP) and receptors (IGF-I- and IGF-II receptor). Their active (unbound) forms exert endocrine and paracrine effects that are required for normal growth and nephron development. We tested the hypothesis that low nephron number is already present during fetal development and expression of important molecules of the IGF-system is altered in MWF.

Methods: We compared MWF and normal Wistar rats during nephrogenesis at day 19 of fetal development (E19) and adult rats at postnatal day 100 (D100). Histomorphometric analysis was performed by stereologic methods. Quantitative mRNA expression was determined by Real-Time PCR.

Results: At E19 glomerular density (-32%) and hepatic mRNA expression of IGF-I (-48%) were decreased, whereas renal mRNA expression of IGF-II receptor (+52%) and IGFBP-3 (+113%) were increased in MWF compared to Wistar (p<0.05, respectively). Systolic blood pressure, urinary albumin excretion, glomerular density, and mean glomerular area were significantly elevated in MWF compared to Wistar at D100 (p<0.05, respectively).

Conclusions: The fetal expression of IGF-system molecules in the MWF model points toward a link between decreased availability of active IGF-I and IGF-II and fetal development of low nephron number with manifestation of genetic hypertension in adult life.