Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/201723
Type: Artigo de periódico
Title: Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.
Author: dos Santos, Alisson F
Almeida, Camila B
Brugnerotto, Ana F
Roversi, Fernanda M
Pallis, Flávia R
Franco-Penteado, Carla F
Lanaro, Carolina
Albuquerque, Dulcinéia M
Leonardo, Flávia C
Costa, Fernando F
Conran, Nicola
Abstract: Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.
Subject: Anemia, Sickle Cell
Angiotensin Ii
Animals
Disease Models, Animal
Dose-response Relationship, Drug
Enzyme-linked Immunosorbent Assay
Gene Expression Regulation
Hydroxyurea
Kidney
Male
Mice
Mice, Inbred C57bl
Mice, Transgenic
Peptidyl-dipeptidase A
Real-time Polymerase Chain Reaction
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Renin-angiotensin System
Angiotensin Ii
Kidneys
Renin–angiotensin System
Sickle Cell Disease
Vasoconstriction
Rights: fechado
Identifier DOI: 10.1016/j.lfs.2014.08.021
Address: http://www.ncbi.nlm.nih.gov/pubmed/25219880
Date Issue: 2014
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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