TY - JOUR
T1 - An angiotensin II type 1 receptor binding molecule has a critical role in hypertension in a chronic kidney disease model
AU - Kobayashi, Ryu
AU - Wakui, Hiromichi
AU - Azushima, Kengo
AU - Uneda, Kazushi
AU - Haku, Sona
AU - Ohki, Kohji
AU - Haruhara, Kotaro
AU - Kinguchi, Sho
AU - Matsuda, Miyuki
AU - Ohsawa, Masato
AU - Toya, Yoshiyuki
AU - Nishiyama, Akira
AU - Yamashita, Akio
AU - Tanabe, Katsuyuki
AU - Maeshima, Yohei
AU - Umemura, Satoshi
AU - Tamura, Kouichi
N1 - Publisher Copyright:
© 2016 International Society of Nephrology
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Angiotensin II type 1 receptor-associated protein (ATRAP) promotes AT1R internalization along with suppression of hyperactivation of tissue AT1R signaling. Here, we provide evidence that renal ATRAP plays a critical role in suppressing hypertension in a mouse remnant kidney model of chronic kidney disease. The effect of 5/6 nephrectomy on endogenous ATRAP expression was examined in the kidney of C57BL/6 and 129/Sv mice. While 129/Sv mice with a remnant kidney showed decreased renal ATRAP expression and developed hypertension, C57BL/6 mice exhibited increased renal ATRAP expression and resistance to progressive hypertension. Consequently, we hypothesized that downregulation of renal ATRAP expression is involved in pathogenesis of hypertension in the remnant kidney model of chronic kidney disease. Interestingly, 5/6 nephrectomy in ATRAP-knockout mice on the hypertension-resistant C57BL/6 background caused hypertension with increased plasma volume. Moreover, in knockout compared to wild-type C57BL/6 mice after 5/6 nephrectomy, renal expression of the epithelial sodium channel α-subunit and tumor necrosis factor-α was significantly enhanced, concomitant with increased plasma membrane angiotensin II type 1 receptor in the kidneys. Thus, renal ATRAP downregulation is involved in the onset and progression of blood pressure elevation caused by renal mass reduction, and implicates ATRAP as a therapeutic target for hypertension in chronic kidney disease.
AB - Angiotensin II type 1 receptor-associated protein (ATRAP) promotes AT1R internalization along with suppression of hyperactivation of tissue AT1R signaling. Here, we provide evidence that renal ATRAP plays a critical role in suppressing hypertension in a mouse remnant kidney model of chronic kidney disease. The effect of 5/6 nephrectomy on endogenous ATRAP expression was examined in the kidney of C57BL/6 and 129/Sv mice. While 129/Sv mice with a remnant kidney showed decreased renal ATRAP expression and developed hypertension, C57BL/6 mice exhibited increased renal ATRAP expression and resistance to progressive hypertension. Consequently, we hypothesized that downregulation of renal ATRAP expression is involved in pathogenesis of hypertension in the remnant kidney model of chronic kidney disease. Interestingly, 5/6 nephrectomy in ATRAP-knockout mice on the hypertension-resistant C57BL/6 background caused hypertension with increased plasma volume. Moreover, in knockout compared to wild-type C57BL/6 mice after 5/6 nephrectomy, renal expression of the epithelial sodium channel α-subunit and tumor necrosis factor-α was significantly enhanced, concomitant with increased plasma membrane angiotensin II type 1 receptor in the kidneys. Thus, renal ATRAP downregulation is involved in the onset and progression of blood pressure elevation caused by renal mass reduction, and implicates ATRAP as a therapeutic target for hypertension in chronic kidney disease.
KW - chronic kidney disease
KW - hypertension
KW - renal tubules
KW - renin–angiotensin system
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U2 - 10.1016/j.kint.2016.10.035
DO - 10.1016/j.kint.2016.10.035
M3 - Article
C2 - 28081856
AN - SCOPUS:85009274788
VL - 91
SP - 1115
EP - 1125
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 5
ER -