Renal damage susceptibility and autoregulation in RF-1 and RF-5 congenic rats. Nephron Exp Nephrol 2005;101(2):e59-66
Date
06/25/2005Pubmed ID
15976509DOI
10.1159/000086417Scopus ID
2-s2.0-23944453877 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
BACKGROUND: Linkage analyses of crosses of rats susceptible to renal damage, fawn-hooded hypertensive (FHH), and those resistant to kidney damage, August x Copenhagen Irish (ACI), indicated that five quantitative trait loci (QTLs), Rf-1 to Rf-5, influence proteinuria (UPV), albuminuria (UAV) and focal glomerulosclerosis (FGS). Here we present data obtained in congenic rats to directly assess the role of the Rf-1 and Rf-5 QTLs.
METHODS: Renal damage (UPV, UAV, and FGS) was assessed in ACI, ACI.FHH-(D1Rat324-D1Rat156)(Rf-1B), and ACI.FHH-(D17Rat117-D17Arb5)(D17Rat180-D17Rat51) (Rf-5) congenic rats in the two-kidney (2K) control situation, and following L-NAME-induced hypertension, unilateral nephrectomy (UNX), and UNX combined with L-NAME. In addition we investigated renal blood flow (RBF) autoregulation in 2K congenic and parental ACI and FHH rats.
RESULTS: Compared to ACI, Rf-1B congenic rats showed a significant increase in susceptibility to renal damage after all three treatments. The increase was most pronounced after UNX with L-NAME. In contrast, the degree of renal damage in Rf-5 congenic rats was not different from the ACI. Like FHH, Rf-1B rats had impaired renal autoregulation. In contrast, RBF autoregulation of Rf-5 rats does not differ from ACI.
CONCLUSION: The Rf-5 QTL does not show any direct effect. The Rf-1 QTL carries one or more genes impairing renal autoregulation and influencing renal damage susceptibility. Whether these are the same genes remains to be established.
Author List
Van Dijk SJ, Specht PA, Lazar J, Jacob HJ, Provoost APMESH terms used to index this publication - Major topics in bold
AlbuminuriaAnimals
Animals, Congenic
Blood Pressure
Chimera
Enzyme Inhibitors
Genetic Predisposition to Disease
Glomerulosclerosis, Focal Segmental
Homeostasis
Hypertension
Kidney Diseases
Male
NG-Nitroarginine Methyl Ester
Nephrectomy
Proteinuria
Quantitative Trait Loci
Rats
Rats, Inbred ACI
Rats, Inbred Strains
Renal Circulation