title: Connexin43-dependent mechanism modulates renin secretion and hypertension.
abstract: To investigate the function of Cx43 during hypertension, we studied the mouse line Cx43KI32 (KI32), in which the coding region of Cx32 replaces that of Cx43. Within the kidneys of homozygous KI32 mice, Cx32 was expressed in cortical and medullary tubules, as well as in some extra- and intraglomerular vessels, i.e., at sites where Cx32 and Cx43 are found in WT mice. Under such conditions, renin expression was much reduced compared with that observed in the kidneys of WT and heterozygous KI32 littermates. After exposure to a high-salt diet, all mice retained a normal blood pressure. However, whereas the levels of renin were significantly reduced in the kidneys of WT and heterozygous KI32 mice, reaching levels comparable to those observed in homozygous littermates, they were not further affected in the latter animals. Four weeks after the clipping of a renal artery (the 2-kidney, 1-clip [2K1C] model), 2K1C WT and heterozygous mice showed an increase in blood pressure and in the circulating levels of renin, whereas 2K1C homozygous littermates remained normotensive and showed unchanged plasma renin activity. Hypertensive, but not normotensive, mice also developed cardiac hypertrophy. The data indicate that replacement of Cx43 by Cx32 is associated with decreased expression and secretion of renin, thus preventing the renin-dependent hypertension that is normally induced in the 2K1C model.
authors.affiliation: Department of Internal Medicine, University Hospital, Lausanne, Switzerland. jacques-antoine.haefliger@chuv.ch
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Krattinger
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Capponi
authors.forename: Britta
authors.initials: B
authors.lastname: Döring
authors.forename: Achim
authors.initials: A
authors.lastname: Plum
authors.forename: Anne
authors.initials: A
authors.lastname: Charollais
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012078:Renal Artery Obstruction; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary; D000097002:Gap Junction beta-1 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D012083:Renin; D012982:Sodium, Dietary; D000097002:Gap Junction beta-1 Protein