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Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin

Item Type:Article
Title:Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin
Creators Name:Lange, S. and Fraune, C. and Alenina, N. and Bader, M. and Danser, A.H.J. and Frenay, A.R. and van Goor, H. and Stahl, R. and Nguyen, G. and Schwedhelm, E. and Wenzel, U.O.
Abstract:BACKGROUND AND OBJECTIVE: The antihypertensive effects of the direct renin inhibitor aliskiren last substantially longer after treatment withdrawal than expected based upon its plasma half-life. This may be attributable to drug accumulation in the kidney as recently shown in rats and mice. Since aliskiren binds to renin we examined in the present study whether this accumulation depends on the renin content of the kidney. METHODS: For this we measured the aliskiren concentration in the kidney of wild-type as well as AT1a receptor and Ren1c mice. AT1a receptor mice overexpress renin due to the lack of angiotensin II-mediated negative feedback, whereas Ren1c mice lack renal renin expression. RESULTS: Accumulation of aliskiren was found in the kidney of wild-type mice. However, renal accumulation was neither influenced by the overexpression nor by the absence of renin in the kidney. It was recently shown that the effects of aliskiren can be blocked by a handle region peptide, which inhibits the nonproteolytic activation of prorenin bound to the (pro)renin receptor. To investigate whether this putative (pro)renin receptor blocker influences renal aliskiren accumulation, we administered the blocker in addition to aliskiren. No influence on renal aliskiren accumulation was observed. CONCLUSION: These data confirm accumulation of aliskiren in the murine kidney and demonstrate that neither renin nor (pro)renin receptor-bound prorenin are major players in this process.
Keywords:Aliskiren, Handle Region Peptide, Kidney, (Pro)Renin Receptor, Renin, Animals, Mice
Source:Journal of Hypertension
ISSN:0263-6352
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:31
Number:4
Page Range:713-719
Date:April 2013
Official Publication:https://doi.org/10.1097/HJH.0b013e32835e226b
PubMed:View item in PubMed

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