ACE inhibitors: Mechanism of action
The RAAS is activated when decreased blood flow is detected in the kidneys, which can happen in normal states such as dehydration but can also happen in pathological states such as heart or liver failure. The RAAS pathway results in the formation of angiotensin II which causes vasoconstriction, as well as activation of aldosterone which is a mineralocorticoid that causes the distal tubules and collecting ducts of the kidneys to reabsorb more sodium at the expense of potassium excretion. This increased vasoconstriction and sodium reabsorption results in higher blood pressure and retention of volume. In a non-pathologic state, higher blood pressure and volume retention is beneficial for organ perfusion and when adequate blood pressure to the kidney is realized, the production of renin will be inhibited in a negative feedback loop. In pathologic states, such as heart or liver failure, the vasoconstriction and volume retention produced by RAAS results in total volume overload and volume redistribution to extravascular tissues, which is why we often see pulmonary edema, ascites, and lower extremity edema in these types of conditions. Due to the underlying pathology in these conditions, which cause decreased blood flow, the RAAS negative feedback loop is inadequately inhibited and the failure to inactivate RAAS often results in decompensated states.
ACE-I has been shown in studies to be beneficial for the treatment in the setting of hypertension, acute myocardial infarction, systolic heart failure, chronic kidney disease and preventing progression of diabetic nephropathy and retinopathy.
Of note: Bradykinin is inactivated by ACE, which is why sometimes people develop bradykinin induced chronic cough with the use of ACE-I.