Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes

• Published in: Scientific reports 2017-03, Vol.7 (1), p.45625-45625, Article 45625
• Main Authors: Begorre, Marc-Antoine, Dib, Abdallah, Habchi, Khalil, Guihot, Anne-Laure, Bourreau, Jennifer, Vessieres, Emilie, Blondeau, Bertrand, Loufrani, Laurent, Chabbert, Marie, Henrion, Daniel, Fassot, Céline
• Format: Article
• Language: English
• Subjects: 59; 631/154/436/2387; 64; 64/60; 692/4019/592/75/593/1920; 96; 96/95; Angiotensin; Angiotensin II; Animals; Anti-inflammatory agents; Arteries; Blood glucose; Creatinine; Cyclooxygenase-2; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - physiopathology; Dilatation, Pathologic - physiopathology; Disease Models, Animal; Glucose tolerance; Humanities and Social Sciences; Inflammation; Inflammation - metabolism; Kidney - blood supply; Kidney - physiopathology; Kidneys; Life Sciences; Male; Mesenteric Arteries - physiopathology; Mice, Transgenic; Microvasculature; Microvessels - physiopathology; multidisciplinary; Oxidative Stress; Oxidizing agents; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - physiology; Renin; Rodents; Science; Streptozocin; Vascular Resistance; Vasodilation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep45625

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 −/y mice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R −/y than in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R −/y mice 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.