505 Review Cell Physiol Biochem 2011;28:505-512 Accepted: October 06, 2011 Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Biochemistr and Biochemistr and Biochemistr and Biochemistr and Biochemistry Copyright © 2011 S. Karger AG, Basel Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2011 S. Karger AG, Basel 1015-8987/11/0283-0505$38.00/0 Accessible online at: www.karger.com/cpb Regulation of Extracellular Fluid Volume and Blood Pressure by Pendrin Juliette Hadchouel 1,2 , Cara Büsst 1,2 , Giuseppe Procino 3 , Giovanna Valenti 3 , Régine Chambrey 4,5 and Dominique Eladari 4,5,6 1 INSERM UMRS 970 - Paris Cardiovascular Research Center (PARCC) and 2 University Paris-Descartes, Paris, 3 Department of General and Environmental Physiology, University of Bary, Bari, 4 Centre de Recherche des Cordeliers, Université Paris Descartes, INSERM UMRS 872, Equipe 3, and 5 Université Pierre et Marie Curie, CNRS ERI 7226, Paris, 6 Department of Physiology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris Dominique Eladari Centre de Recherche des Cordeliers, Equipe 3, 15, rue de l’Ecole de Médecine, F-75270 Paris Cedex 06 (France) Tel. +33 1 55 42 78 63, Fax + 33 1 46 33 41 72 E-Mail dominique.eladari@crc.jussieu.fr Key Words Intercalated cells  NDCBE  AQP5  Distal nephron  Cell volume  ATP Abstract Na + is commonly designed as the culprit of salt-sensitive hypertension but several studies suggest that abnormal Cl - transport is in fact the triggering mechanism. This review focuses on the regulation of blood pressure (BP) by pendrin, an apical Cl - /HCO 3 - exchanger which mediates HCO 3 - secretion and transcellular Cl - transport in type B intercalated cells (B-ICs) of the distal nephron. Studies in mice showed that it is required not only for acid-base regulation but also for BP regulation as pendrin knock-out mice develop hypotension when submitted to NaCl restriction and are resistant to aldosterone-induced hypertension. Pendrin contrib- utes to these processes by two mechanisms. First, pendrin-mediated Cl - transport is coupled with Na + reabsorption by the Na + -dependent Cl - /HCO 3 - exchanger NDCBE to mediate NaCl reabsorption in B-ICs. Second, pendrin activity regulates Na + reab- sorption by the adjacent principal cells, possibly by interaction with the ATP-mediated paracrine signalling recently identified between ICs and principal cells. Interestingly, the water channel AQP5 was recently found to be expressed at the apical side of B-ICs, in the absence of a basolateral water channel, and pendrin and AQP5 membrane expressions are both inhibited by K + depletion, suggesting that pendrin and AQP5 could cooperate to regulate cell volume, a potent stimulus of ATP release. Introduction Arterial hypertension is one of the most common diseases affecting the human population. Hypertension is a complex trait influenced by many environmental and genetic factors acting both alone and in concert. Several organs (e.g. the kidney, heart, vasculature and central nervous system) are involved in the maintenance of blood pressure. Transient disruption of any of these systems can lead to an acute variation in blood pressure.