title: Restoration of connexin 40 (Cx40) in Renin-producing cells reduces the hypertension of Cx40 null mice.
abstract: Connexin 40 (Cx40) is expressed by the renin-producing cells (RSCs) of the kidneys and the endothelial cells of blood vessels. Cx40 null mice (Cx40(-/-)) feature a much increased renin synthesis and secretion, which results in chronic hypertension, and also display an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels and nitric oxide production. To discriminate the effect of Cx40 in renin secretion and vascular signaling, we targeted Cx40 to either the RSCs or the endothelial cells of Cx40 null mice. When compared with Cx40(-/-) controls, the animals expressing Cx40 in RSCs were less hypertensive and featured reduced renin levels, still numerous RSCs outside the wall of the afferent arterioles. In contrast, mice expressing Cx40 in the endothelial cells were as hypertensive as Cx40(-/-) mice, in spite of control levels of Cx37 and eNOS. Our data show that blood pressure is improved by restoration of Cx40 expression in RSCs but not in endothelial cells, stressing the prominent role of renin in the mouse hypertension linked to loss of Cx40.
authors.affiliation: Department of Medicine, Laboratory of Experimental Medicine, c/o Department of Physiology, Bugnon 7a, 1005 Lausanne, Switzerland. Jacques-Antoine.Haefliger@chuv.ch.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Gal
authors.forename: Florian
authors.initials: F
authors.lastname: Alonso
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wagner
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.forename: Denise
authors.initials: D
authors.lastname: Nardelli Haefliger
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D017630:Connexins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042787:Receptor, TIE-2; D012083:Renin; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein; C079086:Tek protein, mouse
keywords: aorta; connexins; endothelial cells; hypertension; kidney; myocytes; renin; smooth muscle