Francesco Trepiccione1, Christelle Soukaseum1, Veronique Baudrie1,2, Yusuke Kumai1, Jacques Teulon3, Bruno Villoutreix4, Nicolas Cornière5, Philine Wangemann6, Andrew J Griffith7, Yoon Byung Choi7, Juliette Hadchouel1, Regine Chambrey1,8, Dominique Eladari5. 1. INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France. 2. Hôpital Européen Georges Pompidou, Département de Physiologie, Assistance Publique-Hopitaux de Paris, Paris, France. 3. CNRS ERL 8228, INSERM UMRS 1138, Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, Paris, France. 4. INSERM U973, MTi-Bioinformatics; University Paris Diderot, Paris, France. 5. Service d'Explorations Fonctionnelles Rénales, Hôpital Felix Guyon, CHU de la Réunion, St Denis, Ile de la Réunion, France. 6. Anatomy and Physiology Department, Kansas State University, Manhattan, KS, USA. 7. Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. 8. Centre National de la Recherche Scientifique, Paris, France.
Abstract
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.
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.
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