Key result
Rf-1B congenic rats showed significantly increased susceptibility to renal damage and impaired renal autoregulation compared to ACI rats, while Rf-5 rats did not differ from ACI.
The Rf-1 QTL, but not Rf-5, carries genes that impair renal autoregulation and increase susceptibility to renal damage in rat models.
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Rat data implicate Rf-1 but not Rf-5 in autoregulation defects; leaves open translation to human hypertensive nephropathy.
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.
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Dijk et al. (2005) studied Renal damage susceptibility and autoregulation. Rf-1B and Rf-5 congenic strains vs. ACI rats was evaluated on Renal damage (proteinuria, albuminuria, focal glomerulosclerosis) and renal blood flow autoregulation. Rf-1B congenic rats showed significantly increased susceptibility to renal damage and impaired renal autoregulation compared to ACI rats, while Rf-5 rats did not differ from ACI.
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