Chromosome 8 replacement in MWF rats suppressed albuminuria by 92% (P<0.005) and restored normal endothelial function, demonstrating partial genetic independence of these traits.
Does replacement of RNO6 or RNO8 with SHR chromosomes improve albuminuria and endothelial dysfunction in MWF rats?
The study demonstrates partial genetic independence of albuminuria and endothelial dysfunction in the MWF rat model, with one locus on RNO8 affecting both.
valor p: p=<0.005
OBJECTIVE: The Munich Wistar Frömter (MWF) rat develops progressive spontaneous albuminuria largely attributable to quantitative trait loci on rat chromosome (RNO)6 and RNO8, respectively. We tested the hypothesis whether quantitative trait loci on these chromosomes are linked to both albuminuria and endothelial dysfunction. METHODS: Experiments were performed in male 12-week-old MWF, Wistar Kyoto (WKY), spontaneously hypertensive rat (SHR) and consomic MWF-6 and MWF-8 rats, in which RNO6 or RNO8 was replaced by the respective SHR chromosome (n = 10 per strain). Vascular function was assessed in aorta and vascular superoxide anion production was determined by confocal microscopy. RESULTS: Acetylcholine potency to induce relaxation was significantly reduced in MWF (6.2 ± 0.1) compared with WKY (7.1 ± 0.1) or SHR (7.3 ± 0.1; P < 0.01). N-nitro-L-arginine methyl ester abolished relaxation to acetylcholine in all three strains, whereas indomethacin exhibited no effect in WKY and MWF. Contractions to noradrenaline and superoxide production were significantly higher in MWF compared with SHR and WKY (P < 0.05, respectively). In consomic MWF-6 and MWF-8 rats albuminuria was markedly suppressed (-85 and -92%, P < 0.005 compared with MWF, respectively). Interestingly, relaxation to acetylcholine and contraction to noradrenaline were restored to normal WKY levels only in MWF-8, but not in MWF-6, due to an increase in stimulated and basal nitric oxide availability, respectively. CONCLUSION: These data demonstrate the partial genetic independence of albuminuria and endothelial dysfunction in this model. From two known albuminuria quantitative trait loci one locus affects both albuminuria and endothelial dysfunction. Whether this observation is based on a common genetic mechanism related to NO availability warrants further investigation.
Steireif et al. (Thu,) conducted a other in Albuminuria and endothelial dysfunction (n=50). Chromosome replacement (consomic MWF-6 and MWF-8 rats) vs. MWF, WKY, and SHR rats was evaluated on Albuminuria suppression and relaxation to acetylcholine (p=<0.005). Chromosome 8 replacement in MWF rats suppressed albuminuria by 92% (P<0.005) and restored normal endothelial function, demonstrating partial genetic independence of these traits.
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