Pharmacological aspects of candesartan, an effective AT1-receptor blocker

Abstract

Blockade of the angiotensin type-1 (AT1) receptor represents a rational therapeutic strategy in cardiovascular disease since it inhibits AT1-receptor-mediated vasoconstriction, cardiovascular remodelling, and vascular inflammation, while preserving AT 2-receptor-mediated vasodilatation and antiproliferative effects. The AT1-receptor blockers currently available bind selectively to the AT1 receptor, but there are marked differences in their affinity for the receptor and their duration of binding. Of the existing agents, candesartan has the highest affinity for the AT1 receptor and has a long duration of binding. Furthermore, candesartan markedly decreases the maximal response to angiotensin II and thus acts as an insurmountable inhibitor; agents such as irbesartan and EXP-3174 (the active metabolite of losartan) can also reduce the maximal response to angiotensin II, although to a lesser extent. In contrast, agents such as losartan act as surmountable inhibitors. These pharmacological differences are reflected in clinically relevant differences regarding the duration of antihypertensive action between agents. In the decade since the introduction of the first AT1-receptor blocker, the therapeutic role of these agents has expanded beyond hypertension to include conditions such as heart failure and diabetic nephropathy. This expanded role reflects the emerging evidence for additional benefits at target organ level that appear to be independent of blood pressure control.