Figure 1

Effects of aldosterone in vascular signaling. Aldosterone activates several pathways in the vasculature, both in endothelial and vascular smooth muscle cells, that interfere with insulin signaling. Aldosterone activates NAD(P)H oxidase-dependent reactive oxygen species (ROS) generation or, more specifically, superoxide anion (O₂^-) generation, which interacts with nitric oxide (NO) forming peroxinitrite (^-ONOO). Aldosterone reduces tetrahydrobiopterin (BH₄), which is an essential NOS cofactor, leading to reduced NO release and impaired vascular relaxation. Aldosterone stimulates mitogen-activated protein kinases (MAPKs) phosphorylation, which leads to activation of proliferative, migratory and inflammatory pathways. Aldosterone activates the formation of hybrid receptors between insulin receptor (IR) and Insulin like Growth Factor-1 receptor (IGF-1R) and induces proteasomal degradation of insulin receptor substrate-1 (IRS-1), decreasing Akt phosphorylation and nitric oxide synthase (NOS) activation. Aldosterone also increases the expression of adhesion molecules, such as vascular cell adhesion molecule 1 (VCAM-1) and Intercellular Adhesion Molecule 1 (ICAM-1), and activates transcription factors, including Nuclear Factor Kappa B (NFkB). Aldosterone increases calcium (Ca⁺²) influx, further decreasing vascular relaxation and favoring contractile responses. (+) indicates activation; (-), inhibition.