Angiotensin II and long-term arterial pressure regulation: The overriding dominance of the kidney

The renin-angiotensin system (RAS) is one of the body's most powerful regul ators of arterial pressure and body fluid volumes. Although the acute effec ts of angiotensin II (AngII), the primary active component of the RAS, on a rterial pressure are mediated primarily by peripheral vasoconstriction, its chronic BP effects are closely intertwined with volume homeostasis, partic ularly with intrarenal actions that influence pressure natriuresis. AngII s hifts pressure natriuresis toward higher BP primarily by increasing tubular reabsorption rather than decreasing GFR. In fact, activation of the RAS ca n serve as an important means of preventing decreases in GFR during volume depletion or circulatory depression. However, with prolonged excess AngII f ormation, particularly in association with hypertension or overperfusion of the kidney, AngII ran contribute to glomerular injury and a gradual loss o f nephron function through its hemodynamic actions. The multiple effects of AngII to increase tubular reabsorption provide a powerful mechanism to pro tect against volume depletion and low BP. However, when AngII levels are in appropriately elevated, this necessitates increased arterial pressure to ma intain sodium and water balance. Blockade of the RAS has proved to be a pow erful therapeutic tool for lowering BP and improving kidney function in dis orders such as hypertension, congestive heart failure, and chronic renal di sease.