RAAS: Clinical Pharmacology

The renin-angiotensin-aldosterone system (RAAS) links kidney perfusion, blood pressure, sodium and water balance, and potassium. Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II, and angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibiting ACE lowers angiotensin II, which reduces vasoconstriction and aldosterone secretion; the lower aldosterone can cause a small increase in serum potassium. ACE is identical to kininase II, so ramipril may also block the breakdown of the vasodepressor peptide bradykinin. How each class acts: - ACE inhibitors (ramipril is the worked example): block the formation of angiotensin II. - Angiotensin II receptor blockers (ARBs; valsartan is the worked example): block the AT1 receptor. - Angiotensin receptor-neprilysin inhibitor (ARNI; sacubitril-valsartan): sacubitril is a prodrug whose active metabolite inhibits neprilysin, which raises natriuretic peptides such as BNP and ANP (vasodilation, natriuresis, diuresis, inhibition of renin and aldosterone release), while valsartan blocks the AT1 receptor. - Mineralocorticoid receptor antagonists (MRAs): spironolactone competitively binds receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted tubule, so more sodium and water are excreted while...