gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

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Identification of gene loci that protect against tubulointerstitial inflammation and microangiopathy in the kidney in severe salt-sensitive hypertension

Genloci schützen die Dahl-Ratte vor tubulointerstitieller Entzündung und Mikroangiopathie

Meeting Abstract (Hypertonie 2004)

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  • P. Kossmehl - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • A.-K. Siegel - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • M. Planert - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • A. Schulz - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • M. Stoll - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • J.A. Bruijn - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • E. de Heer - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden
  • R. Kreutz - Charité-Universitätsmedizin Berlin, Universität Münster, Universität Leiden

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP24

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2004/04hoch024.shtml

Published: August 10, 2005

© 2005 Kossmehl et al.
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Objective: To analyze the influence of genetic factors on renal injury in salt-sensitive hypertension.

Methods: We compared salt-sensitive Dahl rats (SS, n=12) with salt-sensitive hypertension with salt-resistant spontaneously hypertensive rats (SHR, n=12) and performed genome-wide linkage analysis to identify quantitative trait loci (QTL) contributing to salt-induced renal injury in an F2-population derived from SS and SHR (n=230). All animals were treated with a high salt diet (4%) from week 6 to 14. Phenotyping at 15 weeks of age included analysis of blood pressure, urinary albumin excretion (UAE), and histological scoring of renal injury parameters.

Results: In response to high-salt diet SS developed a striking increase in systolic blood pressure and urinary albumin excretion (UAE) compared to SHR (244 +/- 12 vs. 169 +/- 16 mmHg and 260 +/- 55 vs. 1.4 +/- 1.2 mg/24h, p<0.001, respectively). SS developed severe glomerulosclerosis (p<0.05) but only mild forms of microangiopathy, tubulointerstitial fibrosis and inflammation compared to SHR. We detected two QTL with significant linkage to UAE on rat chromosomes (RNO) 6 and 19 (lod score >6, p<0.000001, respectively). Interestingly, some F2-animals demonstrated severe microangiopathy and tubulointerstitial inflammation, that exceeded the mild degree observed in the parental SS strain. Genome-wide QTL analysis revealed 2 loci with suggestive linkage to these phenotypes on RNO3 and RNO5, while no linkage to glomerular damage was found. The maximum effect was found for linkage to tubulointerstitial inflammation on RNO5 (p=0.000085). Further analyses at these loci indicated, that the severity of damage was related to the SHR-allele. Thus, the SS-allele protected against microangiopathy and tubulointerstitial inflammation at these loci.

Conclusion: We identified gene loci that confer protection against the development of microangiopathy and tubulointerstitial inflammation in salt-sensitive hypertension.