Document Detail

Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension.
MedLine Citation:
PMID:  23529167     Owner:  NLM     Status:  MEDLINE    
We have previously shown that angiotensin II type 1 receptor-associated protein (ATRAP/Agtrap) interacts with the angiotensin II type 1 receptor and promotes constitutive internalization of the receptor so as to inhibit the pathological activation of its downstream signaling but preserve baseline physiological signaling activity. The present study was designed to investigate the role of renal ATRAP in angiotensin II-dependent hypertension. We generated transgenic mice dominantly expressing ATRAP in the renal tubules, including renal distal tubules. The renal ATRAP transgenic mice exhibited no significant change in blood pressure at baseline on normal salt diet. However, in the renal ATRAP transgenic mice compared with wild-type mice, the following took place: (1) the development of high blood pressure in response to angiotensin II infusion was significantly suppressed based on radiotelemetry, (2) the extent of daily positive sodium balance was significantly reduced during angiotensin II infusion in metabolic cage analysis, and (3) the renal Na+ -Cl- cotransporter activation and α-subunit of the epithelial sodium channel induction by angiotensin II infusion were inhibited. Furthermore, adenoviral overexpression of ATRAP suppressed the angiotensin II-mediated increase in the expression of α-subunit of the epithelial sodium channel in mouse distal convoluted tubule cells. These results indicate that renal tubule-dominant ATRAP activation provokes no evident effects on blood pressure at baseline but exerts an inhibitory effect on the pathological elevation of blood pressure in response to angiotensin II stimulation, thereby suggesting that ATRAP is a potential target of interest in blood pressure modulation under pathological conditions.
Hiromichi Wakui; Kouichi Tamura; Shin-Ichiro Masuda; Yuko Tsurumi-Ikeya; Megumi Fujita; Akinobu Maeda; Masato Ohsawa; Kengo Azushima; Kazushi Uneda; Miyuki Matsuda; Kenichiro Kitamura; Shinichi Uchida; Yoshiyuki Toya; Hiroyuki Kobori; Kiyotaka Nagahama; Akio Yamashita; Satoshi Umemura
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-25
Journal Detail:
Title:  Hypertension     Volume:  61     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-16     Completed Date:  2013-07-09     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1203-10     Citation Subset:  IM    
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
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MeSH Terms
Adaptor Proteins, Signal Transducing / biosynthesis,  genetics*
Angiotensin II / pharmacology*
Blood Pressure / drug effects
Blotting, Western
DNA / genetics*
Disease Models, Animal
Gene Expression Regulation*
Hypertension / genetics*,  metabolism,  pathology
Kidney Tubules, Distal / metabolism*,  pathology
Mice, Transgenic
Polymerase Chain Reaction
Renin-Angiotensin System / physiology
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Agtrap protein, mouse; 11128-99-7/Angiotensin II; 9007-49-2/DNA
Comment In:
Hypertension. 2013 Jun;61(6):1150-2   [PMID:  23529171 ]

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