Synergistic QTL interactions between Rf-1 and Rf-3 increase renal damage susceptibility in double congenic rats

The FHH (fawn-hooded hypertensive) rat is a model of hypertension-associated chronic kidney damage. Five interacting quantitative trait loci (QTLs), named Rf-1–Rf-5, determine the high renal susceptibility. The aim of the present study was to investigate a possible interaction between Rf-1 and Rf-3....

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Veröffentlicht in:Kidney international Jg. 69; H. 8; S. 1369 - 1376
Hauptverfasser: Van Dijk, S.J., Specht, P.A.C., Lazar, J., Jacob, H.J., Provoost, A.P.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York, NY Elsevier Inc 01.04.2006
Nature Publishing
Elsevier Limited
Schlagworte:
Administration, Oral
Animals
Animals, Congenic
Biological and medical sciences
Blood Pressure - genetics
Chromosome Mapping
Chromosomes, Mammalian
congenic rats
Enzyme Inhibitors - administration & dosage
Follow-Up Studies
Genetic Markers
Genetic Predisposition to Disease
Genome
Homeostasis - genetics
Homozygote
Hypertension, Renal - etiology
Hypertension, Renal - genetics
Kidney Diseases - genetics
Kidney Diseases - physiopathology
L-NAME-hypertension
Male
Medical sciences
Nephrectomy
Nephrology. Urinary tract diseases
NG-Nitroarginine Methyl Ester - administration & dosage
proteinuria
Proteinuria - genetics
Quantitative Trait Loci
Rats
Rats, Inbred ACI
Renal Circulation - genetics
renal damage susceptibility
Survival Analysis
Time Factors
unilateral nephrectomy
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
renal damage susceptibility
L-NAME-hypertension
congenic rats
unilateral nephrectomy
proteinuria
Nephrology
Rat
Quantitative character
Cardiovascular disease
Synergism
Kidney
Urology
Nephrectomy
Surgery
Congenic
Drug interaction
Hypertension
Urinary system disease
Rodentia
Vertebrata
Mammalia
Treatment
Urinary system
Animal
Unilateral
Lesion
Proteinuria
ISSN:0085-2538, 1523-1755
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Zusammenfassung:The FHH (fawn-hooded hypertensive) rat is a model of hypertension-associated chronic kidney damage. Five interacting quantitative trait loci (QTLs), named Rf-1–Rf-5, determine the high renal susceptibility. The aim of the present study was to investigate a possible interaction between Rf-1 and Rf-3. Differences in renal susceptibility between ACI (August × Copenhagen Irish) controls, Rf-1A and Rf-3 single congenics, and Rf-1A+3 double congenic rats were assessed using four different treatments: two-kidney control (2K), 2K plus Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension (2K+L-NAME), unilateral nephrectomy (UNX), and UNX plus L-NAME-induced hypertension (UNX+L-NAME). Proteinuria (UPV) and systolic blood pressure (SBP) were assessed after 6, 12, and 18 weeks, while the incidence of glomerulosclerosis (%FGS) was determined at the end of the experiment. In a separate experiment, renal autoregulation was assessed in 13–15-week old 2K rats of all four strains. Compared to ACI rats, small increases in renal susceptibility were found in Rf-1A and Rf-3 single congenics following 2K+L-NAME, UNX, and UNX+L-NAME treatments. However, in the Rf-1A+3 double congenics, a major increase in renal susceptibility was found with all four treatments. Both Rf-1A and Rf-1A+3 congenic rats had an impaired renal autoregulation. In contrast, the Rf-3 had a normal autoregulation, similar to that of the ACI rat. These findings indicate that Rf-1 and Rf-3 alone slightly increase the susceptibility to the development of renal damage. However, a synergistic interaction between these two QTLs markedly enhances renal susceptibility. In contrast to the Rf-1 region, the Rf-3 region does not carry genes influencing renal autoregulation.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:0085-2538
1523-1755
DOI:10.1038/sj.ki.5000301