Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium

Sontia, B., Montezano, A.C., Paravicini, T., Tabet, F. and Touyz, R.M. (2008) Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium. Hypertension, 51(4), pp. 915-921. (doi: 10.1161/HYPERTENSIONAHA.107.100339)

Abstract

Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg2+ changes are unclear, but the novel Mg2+ transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg2+ administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg2+), (2) Mg2+ group (0.75% dietary Mg2+), (3) aldosterone group (Aldo, 400 μg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg2+ group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na+ was increased and serum K+ and Mg2+ decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg2+ supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg2+ increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure–independent renal and cardiovascular fibrosis and inflammation through Mg2+-sensitive pathways. We suggest that altered Mg2+ metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg2+ protects against cardiovascular and renal damaging actions of aldosterone.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Montezano, Dr Augusto and Touyz, Professor Rhian
• Authors: Sontia, B., Montezano, A.C., Paravicini, T., Tabet, F., and Touyz, R.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• ISSN: 0194-911X
• ISSN (Online): 1524-4563
• Published Online: 11 February 2008