title: Renal tubule angiotensin II type 1 receptor-associated protein promotes natriuresis and inhibits salt-sensitive blood pressure elevation.
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.
  
  
  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: 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.).
authors: Hiromichi
authors: H
authors: Wakui
authors: 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.).
authors: Kazushi
authors: K
authors: Uneda
authors: 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.).
authors: Kouichi
authors: K
authors: Tamura
authors: 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.).
authors: Masato
authors: M
authors: Ohsawa
authors: 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.).
authors: Kengo
authors: K
authors: Azushima
authors: 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.).
authors: Ryu
authors: R
authors: Kobayashi
authors: 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.).
authors: Kohji
authors: K
authors: Ohki
authors: 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.).
authors: Toru
authors: T
authors: Dejima
authors: 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.).
authors: Tomohiko
authors: T
authors: Kanaoka
authors: 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.).
authors: Yuko
authors: Y
authors: Tsurumi-Ikeya
authors: 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.).
authors: Miyuki
authors: M
authors: Matsuda
authors: 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.).
authors: Kotaro
authors: K
authors: Haruhara
authors: Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan (A.N.).
authors: Akira
authors: A
authors: Nishiyama
authors: 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.).
authors: Machiko
authors: M
authors: Yabana
authors: 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.).
authors: Tetsuya
authors: T
authors: Fujikawa
authors: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (A.Y.).
authors: Akio
authors: A
authors: Yamashita
authors: 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.).
authors: Satoshi
authors: S
authors: Umemura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009318:Natriuresis / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D015415:Biomarkers; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D000584:Amiloride
keywords: angiotensin receptors; basic science; gene expression/regulation; hypertension (kidney); receptors; salt‐sensitive; sodium transport (kidney)