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⁺ wasas 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.