Genetic locus on MWF rat chromosome 6 affects kidney damage in response to L-NAME treatment in spontaneously hypertensive rats

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  • Angela Schulz, Charite - Universitatsmedizin Berlin
  • ,
  • Sabrina Schütten, Charite - Universitatsmedizin Berlin
  • ,
  • Leonard Schulte, Charite - Universitatsmedizin Berlin
  • ,
  • Peter Kossmehl, Charite - Universitatsmedizin Berlin
  • ,
  • Jens R. Nyengaard
  • Roland Vetter, Charite - Universitatsmedizin Berlin
  • ,
  • Matthias Huber, Charite - Universitatsmedizin Berlin
  • ,
  • Reinhold Kreutz, Charite - Universitatsmedizin Berlin
  • Good Clinical Practic

A major quantitative trait locus (QTL) on rat chromosome (RNO)6 was linked to albuminuria in Munich Wistar Frömter rats (MWF). We tested whether transfer of MWF RNO6 into the background of albuminuria-resistant spontaneously hypertensive rats (SHR) induces albuminuria in consomic SHR-6MWF animals. Male MWF, SHR, and SHR-6MWF were sham operated and treated between 6 and 24 wk of age with normal water (Sham) or with water containing 20 mg/l NG-nitro-L-arginine methyl ester (L-NAME) or unilaterally nephrectomized (Nx). Compared with SHR albuminuria was not increased in SHR-6MWF in both Sham and Nx groups. All animals survived the observation period in Sham and Nx groups, while premature mortality occurred from 12-14 wk on in L-NAME-treated SHR and SHR-6MWF compared with MWF L-NAME animals, in which survival was not affected (P < 0.005, respectively). Subsequent further analysis of L-NAME-treated animals at 12 wk of age showed significantly increased arterial blood pressures in both SHR and SHR-6MWF compared with control (P < 0.05), with higher levels in SHR compared with consomics (P < 0.05). However, L-NAME-treated consomic animals demonstrated increased albuminuria compared with SHR (12.7 ± 3.5 vs. 0.8 ± 0.2 mg/24 h; P < 0.05) and an induction of tubulointerstitial structural injury and expression of neutrophil gelatinase-associated lipocalin mRNA (P < 0.05 vs. other strains). Our study demonstrates that isolation of the RNO6 albuminuria QTL from the MWF background and transfer into SHR fails to induce an albuminuria phenotype during normal conditions or after nephron reduction. Moreover, our data indicate that genes on RNO6 contribute to the development of L-NAME-induced renal damage in the SHR strain.

Original languageEnglish
JournalPhysiological Genomics
Volume42
Issue1
Pages (from-to)126-133
Number of pages8
ISSN1094-8341
DOIs
Publication statusPublished - 1 Jun 2010

    Research areas

  • Albuminuria, Genetics, Nitric oxide

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