The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys, resulting in augmented blood volume and pressure. Hypertension, or high blood pressure, is often managed with inhibitors targeting different stages of RAAS. Angiotensin II receptor blockers (ARBs) obstruct angiotensin II from binding to receptors, instigating vasodilation and blood pressure reduction. ACE inhibitors hinder the transformation of angiotensin I to angiotensin II, lessening vasoconstriction and fluid volume, thereby lowering blood pressure. However, these inhibitors cannot inhibit ACE-independent pathways mediated by enzymes such as chymase or cathepsin G, which can enable angiotensin II production and its effects. To completely inhibit angiotensin II production, the initial step must be blocked. Direct renin inhibitors, like aliskiren, achieve this by directly binding to renin and preventing the conversion of angiotensinogen to angiotensin I. As a result, angiotensin II production decreases, leading to decreased vasoconstriction and lower blood pressure. Reduced angiotensin II production also diminishes aldosterone secretion, decreasing renal sodium and water reabsorption and reducing blood volume and pressure. However, aliskiren has side effects such as headache, gastroesophageal reflux, dizziness, fatigue, allergic reactions, and angioedema.
