Absence of an interaction between the Rf-1 and Rf-5 QTLs influencing susceptibility to renal damage in rats.
BACKGROUND
Previous studies showed that combining the Rf-1 and Rf-3 or Rf-4 QTLs of FHH induced synergistic interactions markedly enhancing renal susceptibility. The present study aimed to determine the presence of such interaction between the Rf-1 and Rf-5 QTLs.


METHODS
Renal damage susceptibility was assessed in Rf-1B, Rf-1B+5, Rf-1B+4 congenics and ACI control rats in four situations: two-kidney control (2K), unilateral nephrectomy (UNX), L-NAME-induced hypertension (2K+L-NAME) and UNX+L-NAME. Albuminuria (UAV) and systolic blood pressure (SBP) were measured during 18 weeks of follow-up. In separate experiments, renal autoregulation was assessed in 2K rats.


RESULTS
In all four situations, Rf-1B+4 rats developed more severe UAV than ACI, Rf-1B and Rf-1B+5. There were no significant differences in UAV between Rf-1B and Rf-1B+5 rats. In the 2K and UNX situation no differences in SBP were noted between all four strains. With 2K+L-NAME and UNX+L-NAME treatment, SBP in double congenics was higher than that of ACI and Rf-1B rats. Renal autoregulation was similarly impaired in all three congenic strains.


CONCLUSIONS
We conclude that the Rf-5 region, alone or in the presence of Rf-1B, does not affect the development of renal damage. We cannot substantiate that the Rf-5 region contains genes influencing renal damage susceptibility.
van Dijk
Sabine J
SJ
Department of Paediatric Surgery, Erasmus MC, Rotterdam, The Netherlands.
Specht
Patricia A C
PA
Lazar
Jozef
J
Jacob
Howard J
HJ
Provoost
Abraham P
AP
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure; D004791:Enzyme Inhibitors; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology; D006706:Homeostasis; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009392:Nephrectomy; D040641:Quantitative Trait Loci; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D051437:Renal Insufficiency / Q000150:complications* / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D016019:Survival Analysis
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester