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Deletion of the angiotensin II type 1 receptor-associated protein enhances renal sodium reabsorption and exacerbates angiotensin II-mediated hypertension.
Kidney Int. 2014 Sep; 86(3):570-81.KI

Abstract

Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) promotes AT1R internalization along with suppression of pathological activation of tissue AT1R signaling. However, the functional significance of ATRAP in renal sodium handling and blood pressure regulation under pathological stimuli is not fully resolved. Here we show the blood pressure of mice with a gene-targeted disruption of ATRAP was comparable to that of wild-type mice at baseline. However, in ATRAP-knockout mice, angiotensin II-induced hypertension was exacerbated and the extent of positive sodium balance was increased by angiotensin II. Renal expression of the sodium-proton antiporter 3, a major sodium transporter in the proximal tubules, urinary pH, renal angiotensinogen production, and angiotensin II content was unaffected. Stimulation of the renal expression and activity of the epithelial sodium channel (ENaC), a major sodium transporter in the distal tubules, was significantly enhanced by chronic angiotensin II infusion. The circulating and urinary aldosterone levels were comparable. The blood pressure response and renal ENaC expression by aldosterone were not affected. Thus, ATRAP deficiency exacerbated angiotensin II-mediated hypertension by pathological activation of renal tubular AT1R by angiotensin II. This directly stimulates ENaC in the distal tubules and enhances sodium retention in an aldosterone-independent manner.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan.Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan.Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

24694992

Citation

Ohsawa, Masato, et al. "Deletion of the Angiotensin II Type 1 Receptor-associated Protein Enhances Renal Sodium Reabsorption and Exacerbates Angiotensin II-mediated Hypertension." Kidney International, vol. 86, no. 3, 2014, pp. 570-81.
Ohsawa M, Tamura K, Wakui H, et al. Deletion of the angiotensin II type 1 receptor-associated protein enhances renal sodium reabsorption and exacerbates angiotensin II-mediated hypertension. Kidney Int. 2014;86(3):570-81.
Ohsawa, M., Tamura, K., Wakui, H., Maeda, A., Dejima, T., Kanaoka, T., Azushima, K., Uneda, K., Tsurumi-Ikeya, Y., Kobayashi, R., Matsuda, M., Uchida, S., Toya, Y., Kobori, H., Nishiyama, A., Yamashita, A., Ishikawa, Y., & Umemura, S. (2014). Deletion of the angiotensin II type 1 receptor-associated protein enhances renal sodium reabsorption and exacerbates angiotensin II-mediated hypertension. Kidney International, 86(3), 570-81. https://doi.org/10.1038/ki.2014.95
Ohsawa M, et al. Deletion of the Angiotensin II Type 1 Receptor-associated Protein Enhances Renal Sodium Reabsorption and Exacerbates Angiotensin II-mediated Hypertension. Kidney Int. 2014;86(3):570-81. PubMed PMID: 24694992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deletion of the angiotensin II type 1 receptor-associated protein enhances renal sodium reabsorption and exacerbates angiotensin II-mediated hypertension. AU - Ohsawa,Masato, AU - Tamura,Kouichi, AU - Wakui,Hiromichi, AU - Maeda,Akinobu, AU - Dejima,Toru, AU - Kanaoka,Tomohiko, AU - Azushima,Kengo, AU - Uneda,Kazushi, AU - Tsurumi-Ikeya,Yuko, AU - Kobayashi,Ryu, AU - Matsuda,Miyuki, AU - Uchida,Shinichi, AU - Toya,Yoshiyuki, AU - Kobori,Hiroyuki, AU - Nishiyama,Akira, AU - Yamashita,Akio, AU - Ishikawa,Yoshihiro, AU - Umemura,Satoshi, Y1 - 2014/04/02/ PY - 2013/05/02/received PY - 2014/02/07/revised PY - 2014/02/13/accepted PY - 2014/4/4/entrez PY - 2014/4/4/pubmed PY - 2015/6/2/medline SP - 570 EP - 81 JF - Kidney international JO - Kidney Int. VL - 86 IS - 3 N2 - Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) promotes AT1R internalization along with suppression of pathological activation of tissue AT1R signaling. However, the functional significance of ATRAP in renal sodium handling and blood pressure regulation under pathological stimuli is not fully resolved. Here we show the blood pressure of mice with a gene-targeted disruption of ATRAP was comparable to that of wild-type mice at baseline. However, in ATRAP-knockout mice, angiotensin II-induced hypertension was exacerbated and the extent of positive sodium balance was increased by angiotensin II. Renal expression of the sodium-proton antiporter 3, a major sodium transporter in the proximal tubules, urinary pH, renal angiotensinogen production, and angiotensin II content was unaffected. Stimulation of the renal expression and activity of the epithelial sodium channel (ENaC), a major sodium transporter in the distal tubules, was significantly enhanced by chronic angiotensin II infusion. The circulating and urinary aldosterone levels were comparable. The blood pressure response and renal ENaC expression by aldosterone were not affected. Thus, ATRAP deficiency exacerbated angiotensin II-mediated hypertension by pathological activation of renal tubular AT1R by angiotensin II. This directly stimulates ENaC in the distal tubules and enhances sodium retention in an aldosterone-independent manner. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/24694992/Deletion_of_the_angiotensin_II_type_1_receptor_associated_protein_enhances_renal_sodium_reabsorption_and_exacerbates_angiotensin_II_mediated_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)30333-1 DB - PRIME DP - Unbound Medicine ER -