Aldosterone is produced and secreted by the adrenal cortex in response to angiotensin II (AngII) acting through its AT1Rs, which are endogenously expressed in adrenocortical zona glomerulosa (AZG) cells [1, . AT1R is a G protein-coupled receptor (GPCR) that also signals through G protein-independent pathways, a plethora of which are mediated by the scaffolding actions of arrestins (arrs), originally discovered as terminators of GPCR signaling . AngII elicits aldosterone synthesis and secretion via both G proteins and arrs (specifically arr1) . Of note, the prototypic drug of the ARB class losartan appears ineffective at blocking the adrenal arr1-dependent aldosterone production and hence, at suppressing circulating aldosterone . This phenomenon (i.e. failure at suppressing aldosterone) has been observed with several angiotensin receptor blockers (ARBs) clinically and is sometimes referred to as “aldosterone breakthrough” . Together, these findings prompted us to investigate the relative potencies of all ARBs at inhibiting these two signal transducers activated by the AT1R and, consequently, gauge their efficacies at lowering aldosterone in vitro and in vivo.