Aldosterone: Essential for Life but Damaging to the Vascular Endothelium

Figure 1. Multiple pathways coordinate and regulate aldosterone signalling. Multiple stimuli result in aldosterone production within the adrenal glands, the role of localized aldosterone production remains unknown. Circulating aldosterone my act on cell surface MR receptors and GPER in addition to the cytosolic MR receptor. The ‘classical’ aldosterone signalling pathway (via cytosolic MR) is protected from cortisol activation by hydroxysteroid dehydrogenase 2 activity. These complex pathways all represent potential future therapeutic targets.

Figure 2. The glomerular filtration barrier. In the representative diagram, (A) the filtrate passes the layers of the filter. Albumin is largely excluded, as indicated by the local albumin concentration on the right. Electron microscopy (B) demonstrates the functional arrangement of cells within the glomerulus [84]. GBM = glomerular basement membrane, GEnC = glomerular endothelial cells, PFP = podocyte foot process.

Figure 3. A suggested mechanism by which aldosterone may affect immune cell transit. In health, repulsion between the negatively charged glycocalyx of white blood cells and the vessel wall limits their interaction. Given the difference in height, the glycocalyx (∼500 nm) shields selectins (∼40 nm). Glycocalyx damage reduces the negative surface charge and allows for electrostatic attraction of white blood cells to the endothelium, which then mediate receptor–ligand interactions, resulting in tethering, rolling, adhesion, and diapedesis.