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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-20052009-104224
Document
Author
Full name
Alvaro Yogi
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Passaglia, Rita de Cassia Aleixo Tostes (President)
Bendhack, Lusiane Maria
Fortes, Zuleica Bruno
Nouailhetas, Viviane Louise Andree
Rossoni, Luciana Venturini
Title in Portuguese
Mecanismos de regulação e função celular do magnésio na hipertensão induzida pela Aldosterona em um modelo genético de hipomagnesemia: papel dos canais TRPM7.
Keywords in Portuguese
Aldosterona
Estresse oxidativo
Hipertensão arterial
Inflamação
Magnésio
Rim
Abstract in Portuguese
Em células endoteliais e músculo liso vascular, aldosterona regula processos associados ao remodelamento vascular como crescimento, expressão de marcadores inflamatórios e estresse oxidativo. Os mecanismos exatos desses efeitos ainda são desconhecidos, mas é sugerido que o influxo de Mg2+ através recém caracterizados TRPM7 seja importante. O objetivo de nosso estudo foi determinar o papel do Mg2+ na função celular e hipertensão induzida pela aldosterona em camundongos com níveis normais (MgH) e baixos (MgL) de Mg2+. A deficiência de Mg2+ e inibição do TRPM7 aumentaram a ativação de vias pró-inflamatórias e fibrogênicas induzidas pela aldosterona. Nós também demonstramos que a infusão de aldosterona é acompanhada de efeitos deletérios sobre o rim e coração, associados ao estresse oxidativo e alterações na concentração de eletrólitos. Esses resultados fornecem novos mecanismos pelos quais aldosterona modula a função celular e ressaltam a importância do Mg2+ e seus transportadores nesses processos e na hipertensão induzida pela aldosterona.
Title in English
Mechanism of regulation and cell function of magnesium in aldosterone-induced hypertension in a genetic model of hypomagnesemia: role of TRPM7.
Keywords in English
Aldosterone
Hypertension
Inflammation
Kidney
Magnesium
Oxidative stress
Abstract in English
In vascular smooth muscle and endothelial cells, aldosterone induces growth, inflammation and oxidative stress. Exact mechanisms underlying aldo-mediated vascular effects remain unclear, but intracellular magnesium (Mg2+) influx through the novel Mg2+ transporter, TRPM7 may be important. Here we sought to determine the role of Mg2+ in cell function and in aldosterone-induced hypertension in mice genetically bred to have normal (MgH) or low (MgL) intracellular Mg2+ levels. Findings from the present study demonstrate that Mg2+ deficiency and inhibition of TRPM7 amplify aldosterone-induced activation of vascular inflammatory, fibrogenic and growth signaling pathways. We also show that aldosterone infusion in MgH and MgL mice are accompanied by end-organ damage, associated to oxidative stress and changes in electrolytes concentration. Our results provide novel insights into putative mechanisms whereby aldo influences VSMC and EC function and highlights the important role of Mg2+ in the development of aldosterone-induced hypertension.
 
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Publishing Date
2009-05-22
 
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