The renin-angiotensin-aldosterone system begins in the kidney. When renal perfusion pressure falls, when the macula densa detects reduced sodium chloride delivery in the distal tubule, or when sympathetic beta-1 fibers stimulate the juxtaglomerular cells, these cells release renin into the circulation. Renin is an enzyme, not a hormone: it cleaves circulating angiotensinogen, produced by the liver, into angiotensin I, a ten-amino-acid peptide with little biological activity. Angiotensin-converting enzyme, bound to the endothelium of pulmonary and renal vessels, removes two residues from angiotensin I to produce angiotensin II, the principal effector of the cascade.
Angiotensin II acts on two fronts. It binds AT1 receptors on arteriolar smooth muscle, producing vasoconstriction that raises systemic vascular resistance. It also stimulates the zona glomerulosa of the adrenal cortex to secrete aldosterone. Aldosterone acts on the distal nephron, increasing sodium reabsorption through epithelial sodium channels and the sodium-potassium ATPase; water follows sodium osmotically, so extracellular fluid and plasma volume expand. The net result is a slower, sustained defense of blood volume and pressure that complements the rapid sympathetic response.