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Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway
BACKGROUND: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. METHODS: Adult intestine-specific Cckbr-knockout mice (Cckbr(fl/fl) villin-Cre) and Dahl salt-sensitive rats were studied on the ef...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278716/ https://www.ncbi.nlm.nih.gov/pubmed/35674015 http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18791 |
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author | Jiang, Xiaoliang Liu, Yunpeng Zhang, Xin-Yang Liu, Xue Liu, Xing Wu, Xianxian Jose, Pedro A. Duan, Shun Xu, Fu-Jian Yang, Zhiwei |
author_facet | Jiang, Xiaoliang Liu, Yunpeng Zhang, Xin-Yang Liu, Xue Liu, Xing Wu, Xianxian Jose, Pedro A. Duan, Shun Xu, Fu-Jian Yang, Zhiwei |
author_sort | Jiang, Xiaoliang |
collection | PubMed |
description | BACKGROUND: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. METHODS: Adult intestine-specific Cckbr-knockout mice (Cckbr(fl/fl) villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6–7 weeks) on intestinal Na(+/)H(+) exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbr(fl/fl) villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbr(fl/fl) villin mice and SS13(BN) rats. We constructed gastrin-SiO(2) microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation. RESULTS: Gastrin-SiO(2) microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na(+/)H(+) exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na(+/)H(+) exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2. CONCLUSIONS: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO(2) microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects. |
format | Online Article Text |
id | pubmed-9278716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-92787162022-08-02 Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway Jiang, Xiaoliang Liu, Yunpeng Zhang, Xin-Yang Liu, Xue Liu, Xing Wu, Xianxian Jose, Pedro A. Duan, Shun Xu, Fu-Jian Yang, Zhiwei Hypertension Original Articles BACKGROUND: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. METHODS: Adult intestine-specific Cckbr-knockout mice (Cckbr(fl/fl) villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6–7 weeks) on intestinal Na(+/)H(+) exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbr(fl/fl) villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbr(fl/fl) villin mice and SS13(BN) rats. We constructed gastrin-SiO(2) microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation. RESULTS: Gastrin-SiO(2) microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na(+/)H(+) exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na(+/)H(+) exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2. CONCLUSIONS: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO(2) microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects. Lippincott Williams & Wilkins 2022-06-08 2022-08 /pmc/articles/PMC9278716/ /pubmed/35674015 http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18791 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
spellingShingle | Original Articles Jiang, Xiaoliang Liu, Yunpeng Zhang, Xin-Yang Liu, Xue Liu, Xing Wu, Xianxian Jose, Pedro A. Duan, Shun Xu, Fu-Jian Yang, Zhiwei Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title | Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title_full | Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title_fullStr | Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title_full_unstemmed | Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title_short | Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na(+)/H(+) Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway |
title_sort | intestinal gastrin/cckbr (cholecystokinin b receptor) ameliorates salt-sensitive hypertension by inhibiting intestinal na(+)/h(+) exchanger 3 activity through a pkc (protein kinase c)-mediated nherf1 and nherf2 pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278716/ https://www.ncbi.nlm.nih.gov/pubmed/35674015 http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18791 |
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