AII also acts at the subfornical organ in the brain, located outside the blood-brain barrier, to promote the release of ADH (see Plate 3-17) and to stimulate thirst. Moreover, it acts on the adrenal medulla to promote catecholamine release.

Finally, AII also stimulates the release of aldosterone, as mentioned above. The major renal effect of aldosterone is to up-regulate apical ENaC and basolateral Na⁺/K⁺ ATPases in principal cells of the connecting tubule and collecting duct. The result is an increase in sodium reabsorption, which increases the negative charge in the tubular lumen that promotes secretion of potassium. In addition, aldosterone increases synthesis and apical insertion of the NCC Na⁺/Cl⁻ cotransporter in the distal convoluted tubule, further promoting reabsorption of sodium and chloride. Finally, aldosterone also up-regulates apical H⁺ ATPases in type A intercalated cells of the collecting duct, which promotes acid secretion through the mechanisms described in the pages that follow.

In recent years, AII has been recognized to have many additional effects that are still in the process of being characterized. In the heart, for example, AII appears to promote myocyte hypertrophy and fibroblast proliferation, which contribute to the adverse cardiac remodeling that occurs in the setting of systolic dysfunction. Likewise, in the kidney, AII appears to promote inflammation and extracellular matrix production, contributing to the progressive glomerulosclerosis seen in chronic kidney disease. Because of these effects, ACE inhibitors are becoming the standard of care in all patients with heart failure or chronic kidney disease.