Renin-Angiotensin-Aldosterone System

The renin-angiotensin-aldosterone system (RAAS) is a coordinated response to reduced effective circulating volume. A fall in renal perfusion pressure, reduced sodium delivery to the distal nephron, or sympathetic beta-1 stimulation causes juxtaglomerular cells to release renin. Renin cleaves liver-derived angiotensinogen into angiotensin I; angiotensin-converting enzyme (ACE), found abundantly on pulmonary endothelium, converts it to angiotensin II. Angiotensin II restores pressure and circulating volume through several linked actions: systemic vasoconstriction, efferent arteriolar constriction, proximal sodium reabsorption, antidiuretic hormone release, thirst, and adrenal aldosterone secretion. Aldosterone then acts at mineralocorticoid receptors in the distal nephron to retain sodium and water while increasing potassium and hydrogen ion excretion. This response is useful during haemorrhage or dehydration. Persistent activation, however, sustains hypertension, increases intraglomerular pressure, promotes albuminuria, and contributes to cardiac and renal injury. RAAS-blocking drugs exploit that same physiology: they reduce vascular tone and sodium retention, and they lower pressure within the glomerulus. The trade-off is predictable. Renal filtration may fall after treatment begins, and serum potassium may rise.