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.
Department of Pediatric Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. s.vandijk@erasmusmc.nl
Sabine J
SJ
Van Dijk
Patricia A C
PA
Specht
Jozef
J
Lazar
Howard J
HJ
Jacob
Abraham P
AP
Provoost
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