Antihypertensive Drugs: Angiotensin II Receptor Blockers

ARBs like losartan and valsartan compete with angiotensin II for AT1 receptors on vascular smooth muscle, blocking receptor activation. This reduces vasoconstriction, allowing blood vessels to dilate and peripheral resistance to decrease. Additionally, AT1 receptor blockade suppresses aldosterone secretion, decreasing sodium and water reabsorption by the kidneys and lowering blood volume and pressure.

AT1 receptors are Gq protein-coupled receptors on vascular smooth muscle that bind angiotensin II. Activation triggers phospholipase C, releasing IP3 and DAG, which phosphorylate myosin light chains and promote actin-myosin interaction. This causes smooth muscle contraction and blood vessel constriction, increasing peripheral resistance and blood pressure. AT1 activation also stimulates aldosterone secretion, promoting sodium and water retention.

Unlike antihypertensive drugs angiotensin converting enzyme inhibitors, which increase bradykinin levels leading to dry cough, ARBs do not affect bradykinin metabolism. ARBs work exclusively by blocking AT1 receptors, avoiding the side effect of elevated bradykinin that causes airway irritation and persistent cough in ACE inhibitor users.

When ARBs block AT1 receptors, aldosterone secretion decreases. Aldosterone normally promotes sodium and water retention in the kidneys, increasing blood volume and pressure. With reduced aldosterone, sodium and water reabsorption decline, lowering blood volume and subsequently reducing blood pressure through decreased circulating fluid volume.

Angiotensin II binding to AT1 receptors activates phospholipase C, an enzyme coupled to Gq proteins. This releases inositol trisphosphate and diacylglycerol, triggering myosin light chain phosphorylation and actin-myosin interaction. These events cause smooth muscle contraction and blood vessel constriction, increasing peripheral resistance and blood pressure.

Losartan and valsartan are widely used ARBs for treating high blood pressure. Both medications compete with angiotensin II for AT1 receptor binding, effectively blocking receptor activation. By preventing AT1 signaling, these drugs reduce vasoconstriction and aldosterone-mediated sodium and water retention, lowering blood pressure through multiple mechanisms.

When ARBs block AT1 receptors, vasoconstriction decreases and blood vessels dilate. Dilation reduces peripheral resistance, the opposition to blood flow in small arteries and arterioles. Lower peripheral resistance requires less pressure to maintain blood flow, resulting in decreased overall blood pressure throughout the cardiovascular system.