Cardiovascular and renal
inflammation induced by
Aldosterone (Aldo) plays an important role in the pathogenesis of
hypertension and renal
fibrosis.
Toll-like receptor 4 (TLR4) signaling contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced
hypertension and renal damage is not clear. In the current study, rats were treated with Aldo-
salt combined with
TAK-242 (a TLR4 signaling antagonist) for 4 weeks. Hemodynamic, cardiac and renal parameters were assayed at the indicated time. We found that Aldo-
salt-treated rats present cardiac and renal
hypertrophy and dysfunction. Cardiac and renal expression levels of TLR4 as well as levels of molecular markers attesting
inflammation and
fibrosis are increased by Aldo infusion, whereas the treatment of
TAK-242 reverses these alterations.
TAK-242 suppresses cardiac and renal inflammatory
cytokines levels (TNF-a, IL-1β and MCP-1). Furthermore,
TAK-242 inhibits
hypertension, cardiac and renal
fibrosis, and also attenuates the Aldo-induced Epithelial-Mesenchymal Transition (EMT). In experimental
hyperaldosteronism, upregulation of TLR4 is correlated with cardiac and renal
fibrosis and dysfunction, and a TLR4 signaling antagonist,
TAK-242, can reverse these alterations.
TAK-242 may be a therapeutic option for
salt-sensitive
hypertension and renal
fibrosis.