Although currently available angiotensin II type 1 (AT1) receptor blockers (ARBs) share a common mechanism of action, blocking AT1 receptors, their receptor binding kinetics and biological actions are not identical. 1 Two ARBs, namely losartan and candesartan cilexetil, are prodrugs that are converted to active drugs in vivo. After oral administration, losartan undergoes the firstpass metabolism in the liver and is converted into EXP3174, whose affinity to the AT1 receptor is 10 times higher than that of losartan. It should be noted that losartan is not a typical prodrug because it has significant ARB activity and only 14% of the administered dose is converted to EXP3174. 2 This indicates that pharmacological effects of losartan are mediated not only by losartan itself but also by EXP3174 and possibly other metabolites as well. There is growing evidence to suggest that losartan has AT1 receptor–independent actions primarily related to antiinflammatory and antiaggregatory mechanisms (Table). These actions have been speculated to be independent of the AT1 receptor blockade primarily because these properties are not shared by other ARBs, such as candesartan and valsartan, or by angiotensin-converting enzyme inhibitors. Furthermore, losartan blocks vasoconstriction and platelet aggregation induced by the thromboxane A2 (TXA2) analog, U46619, and displaces ligand binding to the TXA2 receptor, suggesting that losartan can act as a dual-receptor antagonist. 3 Interestingly, EXP3174 and irbesartan, another ARB, both of which have the imidazole moiety of biphenyl tetrazole in their structure similar to losartan, interact with the TXA2 receptor. Thus, the chemical structure appears to determine the AT1 receptor–independent actions of the ARBs. 4 However, because stimulation of the AT1 receptor alone is also able to stimulate inflammation and thrombosis through upregulation of inflammatory cytokines and prostaglandins (PGs), 5 the significance of such AT1 receptor–independent actions of losartan over its AT1 receptor antagonism has been difficult to prove.