Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy

J. Lutz, K. Risch, S. Liu, B. Antus, C. Schmaderer, M. Roos, N. Ouyang, M. Lehmann, U. Heemann

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Angiotensin-II (Ang-II) type 1 (AT1) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT1 receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT2) receptors under AT1 receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT 1 blockers most effectively delayed CAN as well as the role of the AT2 receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT1 (candesartan) and/or AT2 (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT1 receptor blockade. A combined AT 1/AT2 blocker treatment reduced CAN similarly to AT 1 blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT1 blocker-treated animals. In summary, AT1 receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT2 receptor does not appear to play an important role in CAN.

Original languageEnglish
Pages (from-to)1080-1088
Number of pages9
JournalKidney International
Volume70
Issue number6
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Angiotensin Type 1 Receptor
Allografts
Apoptosis
Cell Count
Angiotensin Type 2 Receptor
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptors
Inbred F344 Rats
Calcium Channel Blockers
Proteinuria
Transplantation
Kidney
Messenger RNA

Keywords

  • Angiotensin receptors
  • Angiotensin-II
  • Apoptosis
  • Chronic allograft nephropathy
  • Kidney transplantaion

ASJC Scopus subject areas

  • Nephrology

Cite this

Lutz, J., Risch, K., Liu, S., Antus, B., Schmaderer, C., Roos, M., ... Heemann, U. (2006). Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. Kidney International, 70(6), 1080-1088. https://doi.org/10.1038/sj.ki.5001709

Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. / Lutz, J.; Risch, K.; Liu, S.; Antus, B.; Schmaderer, C.; Roos, M.; Ouyang, N.; Lehmann, M.; Heemann, U.

In: Kidney International, Vol. 70, No. 6, 09.2006, p. 1080-1088.

Research output: Contribution to journalArticle

Lutz, J, Risch, K, Liu, S, Antus, B, Schmaderer, C, Roos, M, Ouyang, N, Lehmann, M & Heemann, U 2006, 'Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy', Kidney International, vol. 70, no. 6, pp. 1080-1088. https://doi.org/10.1038/sj.ki.5001709
Lutz, J. ; Risch, K. ; Liu, S. ; Antus, B. ; Schmaderer, C. ; Roos, M. ; Ouyang, N. ; Lehmann, M. ; Heemann, U. / Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. In: Kidney International. 2006 ; Vol. 70, No. 6. pp. 1080-1088.
@article{76ff6356981544609ec5be0d4829d7d4,
title = "Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy",
abstract = "Angiotensin-II (Ang-II) type 1 (AT1) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT1 receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT2) receptors under AT1 receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT 1 blockers most effectively delayed CAN as well as the role of the AT2 receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT1 (candesartan) and/or AT2 (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT1 receptor blockade. A combined AT 1/AT2 blocker treatment reduced CAN similarly to AT 1 blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT1 blocker-treated animals. In summary, AT1 receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT2 receptor does not appear to play an important role in CAN.",
keywords = "Angiotensin receptors, Angiotensin-II, Apoptosis, Chronic allograft nephropathy, Kidney transplantaion",
author = "J. Lutz and K. Risch and S. Liu and B. Antus and C. Schmaderer and M. Roos and N. Ouyang and M. Lehmann and U. Heemann",
year = "2006",
month = "9",
doi = "10.1038/sj.ki.5001709",
language = "English",
volume = "70",
pages = "1080--1088",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy

AU - Lutz, J.

AU - Risch, K.

AU - Liu, S.

AU - Antus, B.

AU - Schmaderer, C.

AU - Roos, M.

AU - Ouyang, N.

AU - Lehmann, M.

AU - Heemann, U.

PY - 2006/9

Y1 - 2006/9

N2 - Angiotensin-II (Ang-II) type 1 (AT1) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT1 receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT2) receptors under AT1 receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT 1 blockers most effectively delayed CAN as well as the role of the AT2 receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT1 (candesartan) and/or AT2 (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT1 receptor blockade. A combined AT 1/AT2 blocker treatment reduced CAN similarly to AT 1 blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT1 blocker-treated animals. In summary, AT1 receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT2 receptor does not appear to play an important role in CAN.

AB - Angiotensin-II (Ang-II) type 1 (AT1) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT1 receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT2) receptors under AT1 receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT 1 blockers most effectively delayed CAN as well as the role of the AT2 receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT1 (candesartan) and/or AT2 (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT1 receptor blockade. A combined AT 1/AT2 blocker treatment reduced CAN similarly to AT 1 blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT1 blocker-treated animals. In summary, AT1 receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT2 receptor does not appear to play an important role in CAN.

KW - Angiotensin receptors

KW - Angiotensin-II

KW - Apoptosis

KW - Chronic allograft nephropathy

KW - Kidney transplantaion

UR - http://www.scopus.com/inward/record.url?scp=33748423224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748423224&partnerID=8YFLogxK

U2 - 10.1038/sj.ki.5001709

DO - 10.1038/sj.ki.5001709

M3 - Article

VL - 70

SP - 1080

EP - 1088

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -