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Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension.
Hypertension. 2013 Jun; 61(6):1203-10.H

Abstract

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.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23529167

Citation

Wakui, Hiromichi, et al. "Enhanced Angiotensin Receptor-associated Protein in Renal Tubule Suppresses Angiotensin-dependent Hypertension." Hypertension (Dallas, Tex. : 1979), vol. 61, no. 6, 2013, pp. 1203-10.
Wakui H, Tamura K, Masuda S, et al. Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension. Hypertension. 2013;61(6):1203-10.
Wakui, H., Tamura, K., Masuda, S., Tsurumi-Ikeya, Y., Fujita, M., Maeda, A., Ohsawa, M., Azushima, K., Uneda, K., Matsuda, M., Kitamura, K., Uchida, S., Toya, Y., Kobori, H., Nagahama, K., Yamashita, A., & Umemura, S. (2013). Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension. Hypertension (Dallas, Tex. : 1979), 61(6), 1203-10. https://doi.org/10.1161/HYPERTENSIONAHA.111.00572
Wakui H, et al. Enhanced Angiotensin Receptor-associated Protein in Renal Tubule Suppresses Angiotensin-dependent Hypertension. Hypertension. 2013;61(6):1203-10. PubMed PMID: 23529167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension. AU - Wakui,Hiromichi, AU - Tamura,Kouichi, AU - Masuda,Shin-Ichiro, AU - Tsurumi-Ikeya,Yuko, AU - Fujita,Megumi, AU - Maeda,Akinobu, AU - Ohsawa,Masato, AU - Azushima,Kengo, AU - Uneda,Kazushi, AU - Matsuda,Miyuki, AU - Kitamura,Kenichiro, AU - Uchida,Shinichi, AU - Toya,Yoshiyuki, AU - Kobori,Hiroyuki, AU - Nagahama,Kiyotaka, AU - Yamashita,Akio, AU - Umemura,Satoshi, Y1 - 2013/03/25/ PY - 2013/3/27/entrez PY - 2013/3/27/pubmed PY - 2013/7/10/medline KW - angiotensin II KW - angiotensin receptors KW - basic science KW - gene expression/regulation KW - hypertension (kidney) KW - membrane transport/ion channels KW - receptors SP - 1203 EP - 10 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 61 IS - 6 N2 - 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. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/23529167/Enhanced_angiotensin_receptor_associated_protein_in_renal_tubule_suppresses_angiotensin_dependent_hypertension_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.111.00572?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -