Elimination of Severe Albuminuria in Aging Hypertensive Rats by Exchange of 2 Chromosomes in Double-Consomic Rats

The inherited nephron deficit and progressive albuminuria development observed in hypertensive Munich Wistar Frömter (MWF) rats are influenced by quantitative trait loci on rat chromosome (RNO) 6 and RNO8. Previous studies in young MWF rats suggested that the nephron deficit represents a cause for glomerular hypertrophy preceding onset of albuminuria at 8 weeks and demonstrated a simultaneous induction of the podocyte stress marker desmin and podoplanin loss in podocytes. Here we investigated the separate genetic influence of RNO6 and RNO8 on early glomerular changes and subsequent albuminuria in single-consomic MWF rats in which RNO6 (MWF-6) and RNO8 (MWF-8) were replaced by the respective spontaneously hypertensive rat (SHR) chromosome. Furthermore, we tested the role of synergistic effects between both chromosomes in a double-consomic MWF-68 strain. Increased glomerular, extramesangial desmin expressions at 6 and albuminuria at 8 weeks were significantly reduced in single- and double-consomics (P