title: Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats.
abstract: Insulin resistance (IR) is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD). On the other hand, amylin has long been related to IR. However the role of amylin in the vascular dysfunction associated to IR is not well addressed. Therefore, the aim of the study was to assess the effect of acute treatment with amylin on endothelium-dependent vasodilation of isolated mesenteric arteries from control (CR) and insulin resistant (IRR) rats and to evaluate the possible mechanisms involved. Five week-old male Wistar rats received 20% D-fructose dissolved in drinking water for 8 weeks and were compared with age-matched CR. Plasmatic levels of glucose, insulin and amylin were measured. Mesenteric microvessels were dissected and mounted in wire myographs to evaluate endothelium-dependent vasodilation to acetylcholine. IRR displayed a significant increase in plasmatic levels of glucose, insulin and amylin and reduced endothelium-dependent relaxation when compared to CR. Acute treatment of mesenteric arteries with r-amylin (40 pM) deteriorated endothelium-dependent responses in CR. Amylin-induced reduction of endothelial responses was unaffected by the H2O2 scavenger, catalase, but was prevented by the extracellular superoxide scavenger, superoxide dismutase (SOD) or the NADPH oxidase inhibitor (VAS2870). By opposite, amylin failed to further inhibit the impaired relaxation in mesenteric arteries of IRR. SOD, or VAS2870, but not catalase, ameliorated the impairment of endothelium-dependent relaxation in IRR. At concentrations present in insulin resistance conditions, amylin impairs endothelium-dependent vasodilation in mircrovessels from rats with preserved vascular function and low levels of endogenous amylin. In IRR with established endothelial dysfunction and elevated levels of amylin, additional exposure to this peptide has no effect on endothelial vasodilation. Increased superoxide generation through NADPH oxidase activity may be a common link involved in the endothelial dysfunction associated to insulin resistance and to amylin exposure in CR.
authors: Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors: Mariam
authors: M
authors: El Assar
authors: Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain.
authors: Javier
authors: J
authors: Angulo
authors: Servicio de Análisis Clínicos del Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors: Marta
authors: M
authors: Santos-Ruiz
authors: Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Paola
authors: P
authors: Moreno
authors: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Anna
authors: A
authors: Novials
authors: Department of Metabolism, Nutrition & Hormones, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors: María Luisa
authors: ML
authors: Villanueva-Peñacarrillo
authors: Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Getafe, Madrid, Spain; Servicio de Geriatría del Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors: Leocadio
authors: L
authors: Rodríguez-Mañas
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: C511179:3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine; D001583:Benzoxazoles; D001786:Blood Glucose; D016166:Free Radical Scavengers; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D014230:Triazoles; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine