Renal damage susceptibility and autoregulation in RF-1 and RF-5 congenic rats.
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.


CONCLUSIONS
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.
Van Dijk
Sabine J
SJ
Department of Pediatric Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. s.vandijk@erasmusmc.nl
Specht
Patricia A C
PA
Lazar
Jozef
J
Jacob
Howard J
HJ
Provoost
Abraham P
AP
D000419:Albuminuria / Q000235:genetics; D000818:Animals; D020296:Animals, Congenic / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D002678:Chimera; D004791:Enzyme Inhibitors; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D006973:Hypertension / Q000209:etiology / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009392:Nephrectomy; D011507:Proteinuria / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000235:genetics*
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester