Mechanism of regulation and cell function of magnesium in aldosterone-induced hypertension in a genetic model of hypomagnesemia: role of TRPM7.

Author(s)

Alvaro Yogi

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2009-03-10

Examining board members

Rita de Cassia Aleixo Tostes Passaglia; Lusiane Maria Bendhack; Zuleica Bruno Fortes; Viviane Louise Andree Nouailhetas; Luciana Venturini Rossoni

• Advisor: Rita de Cassia Aleixo Tostes Passaglia

Abstract

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. (AU)