title: Genetic linkage of albuminuria and renal injury in Dahl salt-sensitive rats on a high-salt diet: comparison with spontaneously hypertensive rats.
abstract: Our aim was to study the effects of high-salt diet on the genetics of albuminuria and renal injury in the Dahl salt-sensitive (SS) rat. We compared SS with salt-resistant spontaneously hypertensive rats (SHR) and with genetically related salt-sensitive stroke-prone SHR (SHRSP). Moreover, we 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). In response to high-salt diet SS and SHRSP developed a striking increase in systolic blood pressure, urinary albumin excretion (UAE), and renal damage indices compared with SHR. Both SHRSP and SS developed severe glomerulosclerosis, whereas microangiopathy, tubulointerstitial fibrosis, and inflammation were more pronounced in SHRSP. We detected two QTL with significant linkage to UAE on rat chromosomes (RNO) 6 and 19. Comparison with the recently identified salt-independent UAE QTL in young animals revealed that the UAE QTL on RNO6 is unique to high-salt conditions, whereas RNO19 plays a significant role during both low- and high-salt conditions. Some F2 animals demonstrated severe microangiopathy and tubulointerstitial injury, which exceeded the degree observed in the parental SS strain. Three loci demonstrated suggestive linkage to these phenotypes on RNO3, RNO5, and RNO20, whereas no linkage to glomerular damage was found. Further analyses at these loci indicated that the severity of renal injury was attributable to the SHR allele. Our data suggest that the SHR genetic background confers greater susceptibility for the development of microangiopathy and tubulointerstitial injury in salt-sensitive hypertension than the SS background.
authors.affiliation: Institut für Klinische Pharmakologie und Toxikologie, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anja-Kristin
authors.initials: AK
authors.lastname: Siegel
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Michael
authors.initials: M
authors.lastname: Planert
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000419:Albuminuria / Q000235:genetics*; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D008040:Genetic Linkage / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics*; D011918:Rats, Inbred SHR / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013599:Systole
chemical_list: D017673:Sodium Chloride, Dietary