the heart, aortic fibrosis and remodeling, and renal injury. 17–23 Work, completed over the last decade, established a critical role for inflammation in initiating fibrosis and remodeling in response to exogenous aldosterone or MR activation. For example, Fiebeler et al24 investigated the contribution of MR activation to proinflammatory and profibrotic mediators in the heart of rats doubly transgenic for the human renin and angiotensinogen genes. MR antagonism prevented vascular injury and cardiac fibrosis, activation of activator protein-1 and NF-κB, and upregulation of basic fibroblast growth factor in the hearts of rats doubly transgenic for the human renin and angiotensinogen genes. Rocha et al25 demonstrated that 4-week treatment with aldosterone and salt caused extensive inflammatory arterial lesions with perivascular macrophages in the heart. MR blockade decreased this inflammatory response. Aldosterone/salt also increased the expression of intercellular adhesion molecule, cyclooxygenase-2, osteopontin, and MCP-1, effects that were decreased by MR blockade.

MR antagonism decreases aortic inflammation, fibrosis, and hypertrophy in hypertensive rats. 21, 23, 26 MR antagonism decreases oxidative stress and inflammation, as measured by tumor necrosis factor-α and MCP-1 expression, in apolipoprotein E–deficient mice fed a high-cholesterol diet, a model of atherosclerosis. 27 Furthermore, like Ang II, the mineralocorticoid deoxycorticosterone acetate causes aortic superoxide production and hypertension through a T-cell–dependent mechanism. 16