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Renal tubule angiotensin II type 1 receptor-associated protein promotes natriuresis and inhibits salt-sensitive blood pressure elevation.
J Am Heart Assoc. 2015 Mar 19; 4(3):e001594.JA

Abstract

BACKGROUND

Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP; Agtrap gene) promotes AT1R internalization along with suppression of pathological AT1R activation. In this study, we examined whether enhancement of ATRAP in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (HS) loading, using ATRAP transgenic mice on a salt-sensitive C57BL/6J background.

METHODS AND RESULTS

Renal ATRAP transgenic (rATRAP-Tg) mice, which exhibit renal tubule-dominant ATRAP enhancement, and their wild-type littermate C57BL/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary HS loading (4% NaCl) for 7 days. In rATRAP-Tg mice, the dietary HS loading-mediated blood pressure elevation was suppressed compared with wild-type mice, despite similar baseline blood pressure. Although renal angiotensin II level was comparable in rATRAP-Tg and wild-type mice with and without HS loading, urinary sodium excretion in response to HS loading was significantly enhanced in the rATRAP-Tg mice. In addition, functional transport activity of the amiloride-sensitive epithelial Na(+) channel was significantly decreased under saline volume-expanded conditions in rATRAP-Tg mice compared with wild-type mice, without any evident change in epithelial Na(+) channel protein expression. Plasma membrane AT1R expression in the kidney of rATRAP-Tg mice was decreased compared with wild-type mice.

CONCLUSIONS

These results demonstrated that distal tubule-dominant enhancement of ATRAP inhibits pathological renal sodium reabsorption and blood pressure elevation in response to HS loading. The findings suggest that ATRAP-mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt-sensitive blood pressure regulation.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan (A.N.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.Y.).Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan (H.W., K.U., K.T., M.O., K.A., R.K., K.O., T.D., T.K., Y.T.I., M.M., K.H., M.Y., T.F., S.U.).

Pub Type(s)

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

Language

eng

PubMed ID

25792129

Citation

Wakui, Hiromichi, et al. "Renal Tubule Angiotensin II Type 1 Receptor-associated Protein Promotes Natriuresis and Inhibits Salt-sensitive Blood Pressure Elevation." Journal of the American Heart Association, vol. 4, no. 3, 2015, pp. e001594.
Wakui H, Uneda K, Tamura K, et al. Renal tubule angiotensin II type 1 receptor-associated protein promotes natriuresis and inhibits salt-sensitive blood pressure elevation. J Am Heart Assoc. 2015;4(3):e001594.
Wakui, H., Uneda, K., Tamura, K., Ohsawa, M., Azushima, K., Kobayashi, R., Ohki, K., Dejima, T., Kanaoka, T., Tsurumi-Ikeya, Y., Matsuda, M., Haruhara, K., Nishiyama, A., Yabana, M., Fujikawa, T., Yamashita, A., & Umemura, S. (2015). Renal tubule angiotensin II type 1 receptor-associated protein promotes natriuresis and inhibits salt-sensitive blood pressure elevation. Journal of the American Heart Association, 4(3), e001594. https://doi.org/10.1161/JAHA.114.001594
Wakui H, et al. Renal Tubule Angiotensin II Type 1 Receptor-associated Protein Promotes Natriuresis and Inhibits Salt-sensitive Blood Pressure Elevation. J Am Heart Assoc. 2015 Mar 19;4(3):e001594. PubMed PMID: 25792129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal tubule angiotensin II type 1 receptor-associated protein promotes natriuresis and inhibits salt-sensitive blood pressure elevation. AU - Wakui,Hiromichi, AU - Uneda,Kazushi, AU - Tamura,Kouichi, AU - Ohsawa,Masato, AU - Azushima,Kengo, AU - Kobayashi,Ryu, AU - Ohki,Kohji, AU - Dejima,Toru, AU - Kanaoka,Tomohiko, AU - Tsurumi-Ikeya,Yuko, AU - Matsuda,Miyuki, AU - Haruhara,Kotaro, AU - Nishiyama,Akira, AU - Yabana,Machiko, AU - Fujikawa,Tetsuya, AU - Yamashita,Akio, AU - Umemura,Satoshi, Y1 - 2015/03/19/ PY - 2015/3/21/entrez PY - 2015/3/21/pubmed PY - 2016/3/2/medline KW - angiotensin receptors KW - basic science KW - gene expression/regulation KW - hypertension (kidney) KW - receptors KW - salt‐sensitive KW - sodium transport (kidney) SP - e001594 EP - e001594 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 4 IS - 3 N2 - BACKGROUND: Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP; Agtrap gene) promotes AT1R internalization along with suppression of pathological AT1R activation. In this study, we examined whether enhancement of ATRAP in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (HS) loading, using ATRAP transgenic mice on a salt-sensitive C57BL/6J background. METHODS AND RESULTS: Renal ATRAP transgenic (rATRAP-Tg) mice, which exhibit renal tubule-dominant ATRAP enhancement, and their wild-type littermate C57BL/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary HS loading (4% NaCl) for 7 days. In rATRAP-Tg mice, the dietary HS loading-mediated blood pressure elevation was suppressed compared with wild-type mice, despite similar baseline blood pressure. Although renal angiotensin II level was comparable in rATRAP-Tg and wild-type mice with and without HS loading, urinary sodium excretion in response to HS loading was significantly enhanced in the rATRAP-Tg mice. In addition, functional transport activity of the amiloride-sensitive epithelial Na(+) channel was significantly decreased under saline volume-expanded conditions in rATRAP-Tg mice compared with wild-type mice, without any evident change in epithelial Na(+) channel protein expression. Plasma membrane AT1R expression in the kidney of rATRAP-Tg mice was decreased compared with wild-type mice. CONCLUSIONS: These results demonstrated that distal tubule-dominant enhancement of ATRAP inhibits pathological renal sodium reabsorption and blood pressure elevation in response to HS loading. The findings suggest that ATRAP-mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt-sensitive blood pressure regulation. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/25792129/Renal_tubule_angiotensin_II_type_1_receptor_associated_protein_promotes_natriuresis_and_inhibits_salt_sensitive_blood_pressure_elevation_ L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.114.001594?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -