1. Acute genetic ablation of pendrin lowers blood pressure in mice
- Author
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Philine Wangemann, Régine Chambrey, Dominique Eladari, Francesco Trepiccione, Véronique Baudrie, Jacques Teulon, Juliette Hadchouel, Andrew J. Griffith, Bruno O. Villoutreix, Yoon Byung Choi, Christelle Soukaseum, Nicolas Cornière, Yusuke Kumai, Trepiccione, Francesco, Soukaseum, Christelle, Baudrie, Veronique, Kumai, Yusuke, Teulon, Jacque, Villoutreix, Bruno, Cornière, Nicola, Wangemann, Philine, Griffith, Andrew J, Byung Choi, Yoon, Hadchouel, Juliette, Chambrey, Regine, Eladari, Dominique, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Molécules Thérapeutiques in silico (MTI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Kansas State University, and National Institutes of Health [Bethesda] (NIH)
- Subjects
Male ,Genetically modified mouse ,medicine.medical_specialty ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Anion Transport Proteins ,030232 urology & nephrology ,Blood Pressure ,Mice, Transgenic ,030204 cardiovascular system & hematology ,Chloride ,Mice ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,In vivo ,Internal medicine ,Extracellular fluid ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,medicine ,otorhinolaryngologic diseases ,Animals ,Diuretic ,Pendrin ,Transplantation ,Kidney ,biology ,business.industry ,Reabsorption ,Original Articles ,diuretics ,Connecting tubule ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Endocrinology ,Blood pressure ,medicine.anatomical_structure ,Sulfate Transporters ,Nephrology ,intercalated cells ,Hypertension ,biology.protein ,business ,Intercalated cell - Abstract
International audience; Background: Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure.Methods: Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued. Therefore, our genetic strategy allows us to test selectively the acute effects of loss of pendrin function.Results: We show that acute loss of pendrin leads to a significant decrease of blood pressure. In addition, acute ablation of pendrin did not alter significantly the acid-base status or blood K + concentration.Conclusion: By using a transgenic mouse model, avoiding off-target effects related to pharmacological compounds, this study suggests that pendrin could be a novel target to treat hypertension.
- Published
- 2017