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

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Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin. / Lange, Sascha; Fraune, Christoph; Alenina, Natalia; Bader, Michael; Danser, A H Jan; Frenay, Anne-Roos; van Goor, Harry; Stahl, Rolf; Nguyen, Genevieve; Schwedhelm, Edzard; Wenzel, Ulrich Otto.

In: J HYPERTENS, Vol. 31, No. 4, 01.04.2013, p. 713-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lange, S, Fraune, C, Alenina, N, Bader, M, Danser, AHJ, Frenay, A-R, van Goor, H, Stahl, R, Nguyen, G, Schwedhelm, E & Wenzel, UO 2013, 'Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin', J HYPERTENS, vol. 31, no. 4, pp. 713-9. https://doi.org/10.1097/HJH.0b013e32835e226b

APA

Lange, S., Fraune, C., Alenina, N., Bader, M., Danser, A. H. J., Frenay, A-R., van Goor, H., Stahl, R., Nguyen, G., Schwedhelm, E., & Wenzel, U. O. (2013). Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin. J HYPERTENS, 31(4), 713-9. https://doi.org/10.1097/HJH.0b013e32835e226b

Vancouver

Lange S, Fraune C, Alenina N, Bader M, Danser AHJ, Frenay A-R et al. Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin. J HYPERTENS. 2013 Apr 1;31(4):713-9. https://doi.org/10.1097/HJH.0b013e32835e226b

Bibtex

@article{d5a34ed5ba0e4d7c87d1007322425572,
title = "Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin",
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 = "Amides, Animals, Antihypertensive Agents, Fumarates, Humans, Immunohistochemistry, Kidney, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Binding, Renin",
author = "Sascha Lange and Christoph Fraune and Natalia Alenina and Michael Bader and Danser, {A H Jan} and Anne-Roos Frenay and {van Goor}, Harry and Rolf Stahl and Genevieve Nguyen and Edzard Schwedhelm and Wenzel, {Ulrich Otto}",
year = "2013",
month = apr,
day = "1",
doi = "10.1097/HJH.0b013e32835e226b",
language = "English",
volume = "31",
pages = "713--9",
journal = "J HYPERTENS",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

RIS

TY - JOUR

T1 - Aliskiren accumulation in the kidney: no major role for binding to renin or prorenin

AU - Lange, Sascha

AU - Fraune, Christoph

AU - Alenina, Natalia

AU - Bader, Michael

AU - Danser, A H Jan

AU - Frenay, Anne-Roos

AU - van Goor, Harry

AU - Stahl, Rolf

AU - Nguyen, Genevieve

AU - Schwedhelm, Edzard

AU - Wenzel, Ulrich Otto

PY - 2013/4/1

Y1 - 2013/4/1

N2 - 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.

AB - 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.

KW - Amides

KW - Animals

KW - Antihypertensive Agents

KW - Fumarates

KW - Humans

KW - Immunohistochemistry

KW - Kidney

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Protein Binding

KW - Renin

U2 - 10.1097/HJH.0b013e32835e226b

DO - 10.1097/HJH.0b013e32835e226b

M3 - SCORING: Journal article

C2 - 23407438

VL - 31

SP - 713

EP - 719

JO - J HYPERTENS

JF - J HYPERTENS

SN - 0263-6352

IS - 4

ER -