title: Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes.
abstract: Diabetes Mellitus is associated with severe cardiovascular disorders involving the renin-angiotensin system, mainly through activation of the angiotensin II type 1 receptor (AT1R). Although the type 2 receptor (AT2R) opposes the effects of AT1R, with vasodilator and anti-trophic properties, its role in diabetes is debatable. Thus we investigated AT2R-mediated dilatation in a model of type 1 diabetes induced by streptozotocin in 5-month-old male mice lacking AT2R (AT2R-/y). Glucose tolerance was reduced and markers of inflammation and oxidative stress (cyclooxygenase-2, gp91phox p22phox and p67phox) were increased in AT2R-/ymice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R-/ythan in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R-/ymice compared to diabetic WT mice. AT2R-dependent dilatation in both isolated mesenteric resistance arteries and perfused kidneys was greater in diabetic mice than in non-diabetic animals. Thus, in type 1 diabetes, AT2R may reduce glycaemia and display anti-oxidant and/or anti-inflammatory properties in association with greater vasodilatation in mesenteric arteries and in the renal vasculature, a major target of diabetes. Therefore AT2R might represent a new therapeutic target in diabetes.
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Begorre
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Dib
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Habchi
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Guihot
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.|CARFI (Cardiovascular Function In Vitro) facility, Angers, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bourreau
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.|CARFI (Cardiovascular Function In Vitro) facility, Angers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vessieres
authors.affiliation: INSERM UMRS 872, Cordeliers Research Centre, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Blondeau
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.|University Hospital (CHU) of Angers, Angers, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Loufrani
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Chabbert
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.|CARFI (Cardiovascular Function In Vitro) facility, Angers, France.|University Hospital (CHU) of Angers, Angers, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.affiliation: CNRS UMR 6015, Angers, France.|INSERM U1083, Angers, France.|MITOVASC Institute, Angers University, Angers, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Fassot
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004108:Dilatation, Pathologic / Q000503:physiopathology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D008822:Mice, Transgenic; D055806:Microvessels / Q000503:physiopathology*; D018384:Oxidative Stress; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D014655:Vascular Resistance
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2