ARBs antagonise the action of angiotensin II in a highly selective manner at the angiotensin II AT1-receptor. Angiotensin II receptors are subclassified into AT1 and AT2 receptors. The AT1-receptor mediates all the classical effects of angiotensin II e.g. vasoconstriction, aldosterone release, sympathetic activation and other potentially harmful effects on the cardiovascular system. The functional role of the AT2-receptor is unclear. Because many tissues contain enzymic pathways capable of converting angiotensin I to angiotensin II independent of angiotensin converting enzyme (ACE), there are theoretical advantages in blocking the renin-angiotensin system via the AT1-receptor compared with ACE inhibition. Many ARBs or active metabolites bind to the AT1-receptor in a manner which is competitive but slowly surmountable, so that duration of action is prolonged. Reduction in blood pressure secondary to vasodilation following angiotensin receptor blockade is greatest when the renin-angiotensin system is activated (e.g. following diuretic therapy or renal artery stenosis) but ARBs also lower blood pressure when there is normal or low activity of the renin-angiotensin system. Nevertheless, Afro-Caribbeans and elderly individuals, who tend to have low renin hypertension, respond less well to monotherapy with ARBs.
đang được dịch, vui lòng đợi..