Name: KAROLINI ZUQUI NUNES
Publication date: 30/07/2018
Advisor:
Name |
Role |
|---|---|
| DALTON VALENTIM VASSALLO | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| DALTON VALENTIM VASSALLO | Advisor * |
| MAYLLA RONACHER SIMÕES | Internal Examiner * |
| MIRIAN FIORESI | External Examiner * |
Summary: Copper homeostasis is essential for the proper functioning of the body. The deficiency and the overload of this metal can lead to the development of pathologies, including the cardiovascular system. The mechanisms involved in vascular changes promoted in situations of copper toxicity are not known. Therefore, in this study we investigated the changes in vascular reactivity promoted by copper (Cu) overload. Thoracic aorta obtained from male Wistar rats was cut into rings and exposed for 1h to 10μg/mLCuCl2. Exposure to Cu decreased the contractile responses of aortic rings to phenylephrine (PHE). Removal of the endothelium and subsequent administration of, N-nitro-L arginine methyl ester (L-NAME), tetrahydrobiopterin (BH4), aminoguanidine, diethyldithiocarbamic acid (DETCA), catalase or tetraethylammonium (TEA), increased contractile responses fenilefrina (Ct L-NAME: 135 ± 8,1 vs Cu L-NAME: 156 ± 12,1; Ct BH4: 99 ± 6,9 vs Cu BH4: 104 ± 3,5; Ct Aminoguanidine: 90 ± 8,3 vs Cu Aminoguanidine: 96 ± 6,8; Ct DETCA: 117 ± 3,2 vs Cu DETCA: 154 ± 14,1; Ct Catalase: 109 ± 6,2 vs Cu Catalase: 113 ± 9,3; Ct TEA: 110 ± 16 vs Cu TEA: 121 ± 12,1). Incubation with apocinyn and tiron enhanced the sensitivity to PHE (Ct Apocinyn: 5,5 ± 0,2 vs Cu Apocinyn: 6,8 ± 0,3; Ct Tiron: 6,7 ± 0,06 vs Cu Tiron: 6,8 ± 0,3). Results demonstrated that high concentrations of Cu reduced PHE-induced vascular reactivity which was associated with an increased production of nitric oxide (NO), attributed to the activation of the inducible nitric oxide synthase and elevated levels of hydrogen peroxide probably related to a rise in superoxide dismutase (SOD) activity and reactive oxygen species (ROS) generation. These effects of copper overload suggest that this metal is a risk factor for cardiovascular disease.
