title: H,K-ATPase type 2 contributes to salt-sensitive hypertension induced by K(+) restriction.
abstract: In industrialized countries, a large part of the population is daily exposed to low K(+) intake, a situation correlated with the development of salt-sensitive hypertension. Among many processes, adaptation to K(+)-restriction involves the stimulation of H,K-ATPase type 2 (HKA2) in the kidney and colon and, in this study, we have investigated whether HKA2 also contributes to the determination of blood pressure (BP). By using wild-type (WT) and HKA2-null mice (HKA2 KO), we showed that after 4 days of K(+) restriction, WT remain normokalemic and normotensive (112 ± 3 mmHg) whereas HKA2 KO mice exhibit hypokalemia and hypotension (104 ± 2 mmHg). The decrease of BP in HKA2 KO is due to the absence of NaCl-cotransporter (NCC) stimulation, leading to renal loss of salt and decreased extracellular volume (by 20 %). These effects are likely related to the renal resistance to vasopressin observed in HKA2 KO that may be explained, in part by the increased production of prostaglandin E2 (PGE2). In WT, the stimulation of NCC induced by K(+)-restriction is responsible for the elevation in BP when salt intake increases, an effect blunted in HKA2-null mice. The presence of an activated HKA2 is therefore required to limit the decrease in plasma [K(+)] but also contributes to the development of salt-sensitive hypertension.
authors: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France.|CNRS ERL 8228 - Centre de Recherche des Cordeliers - Laboratoire de Métabolisme et Physiologie Rénale, F-75006, Paris, France.
authors: Christine
authors: C
authors: Walter
authors: Faculté des Sciences de Tunis El Manar, Campus Universitaire 2092, El Manar Tunis, Tunisie.
authors: Mariem Ben
authors: MB
authors: Tanfous
authors: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France.|CNRS ERL 8228 - Centre de Recherche des Cordeliers - Laboratoire de Métabolisme et Physiologie Rénale, F-75006, Paris, France.
authors: Katia
authors: K
authors: Igoudjil
authors: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France.|CNRS ERL 8228 - Centre de Recherche des Cordeliers - Laboratoire de Métabolisme et Physiologie Rénale, F-75006, Paris, France.
authors: Amel
authors: A
authors: Salhi
authors: Departement für Nephrologie, Hypertonie und klinische Pharmakologie, Universitätsspital Bern - Inselspital, CH-3010, Bern, Switzerland.
authors: Geneviève
authors: G
authors: Escher
authors: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France. gilles.crambert@crc.jussieu.fr.|CNRS ERL 8228 - Centre de Recherche des Cordeliers - Laboratoire de Métabolisme et Physiologie Rénale, F-75006, Paris, France. gilles.crambert@crc.jussieu.fr.
authors: Gilles
authors: 0000-0001-7065-9124
authors: G
authors: Crambert
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015232:Dinoprostone / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000097:blood / Q000378:metabolism*; D011191:Potassium Deficiency / Q000150:complications / Q000378:metabolism*; D064486:Solute Carrier Family 12, Member 3 / Q000378:metabolism; D014667:Vasopressins / Q000097:blood
chemical_list: C578875:Slc12a3 protein, mouse; D064486:Solute Carrier Family 12, Member 3; D014667:Vasopressins; C000620945:ATP12A protein, mouse; D017506:H(+)-K(+)-Exchanging ATPase; D015232:Dinoprostone; D011188:Potassium
keywords: Blood pressure; Extracellular volume; Low-K+ diet; Na+/Cl−-cotransporter; Vasopressin