Angiotensin II Type 1 Receptor Antagonists

     AT1 receptor antagonists, also termed angiotensin receptor blockers (ARBs), are a second group of drugs that interfere with the renin–angiotensin system. There are at least two distinct types of AII receptors: AT1 and AT2. All the actions of AII known to affect blood pressure control (e.g., vasoconstriction, aldosterone release, renal Na reabsorption, and sympathetic nervous system stimulation) are mediated by its binding to receptors of the AT1 subtype. The AT2 receptor subtype is abundant during fetal development and has been located in some adult tissues, but its precise actions
are unknown.
     ARBs compete with AII for AT1 receptors and therefore inhibit AII-mediated effects, thus lowering the blood pressure of hypertensive patients. ARBs provide a more substantial blockade of the renin–angiotensin system than ACE inhibitors, because the latter do not completely block formation of AII (some AI is converted to AII by circulating enzymes other than ACE). Unlike ACE inhibitors, the AT1 receptor antagonists do not affect serum BK levels.
     Each of ARBs is excreted primarily in the bile but most are also partly excreted in the urine. Trials have demonstrated that ARBs are as effective as ACE inhibitors in treating hypertension, and they are among the best tolerated antihypertensive drugs. As with ACE inhibitors, the blood pressure–lowering effect of ARBs is enhanced by concurrent use of a thiazide diuretic. Also like ACE inhibitors, ARBs
have the potential side effects of hypotension and hyperkalemia (owing to reduced aldosterone levels). Unlike ACE inhibitors, ARBs typically do not cause cough.
     In the setting of moderate to severe heart failure, ARBs display hemodynamic benefi ts similar to those of ACE inhibitors. Thus, ARBs are generally recommended in heart failure for patients who are intolerant of ACE inhibitors (e.g., because of ACE inhibitor–induced cough). Studies in patients with type 2 diabetes have demonstrated that ARBs slow the progression of kidney disease, an effect that also has been demonstrated with ACE inhibitors.
     In addition to ACE inhibitors and ARBs, other antagonists of the renin–angiotensin system in the treatment of hypertension include the direct renin inhibitor aliskiren and aldosterone receptor antagonists.