Key result
The study investigated the relative potencies of angiotensin receptor blockers at inhibiting AT1R signal transducers and lowering aldosterone in vitro and in vivo, though no results were reported in the abstract.
Why the study?
Do different ARBs vary in their ability to inhibit β-arrestin1-dependent aldosterone production and prevent aldosterone breakthrough?
Do different ARBs vary in their ability to inhibit β-arrestin1-dependent aldosterone production and prevent aldosterone breakthrough?
This study investigates the mechanistic basis of 'aldosterone breakthrough' by evaluating the efficacy of various ARBs in blocking β-arrestin1-dependent aldosterone production.
Leaves open whether ARBs differ in β-arrestin1-mediated aldosterone inhibition; animal findings require human confirmation before clinical consideration.
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.
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A 2016 study studied this question. Angiotensin receptor blockers (ARBs) was evaluated on Relative potencies of ARBs at inhibiting AT1R signal transducers and lowering aldosterone in vitro and in vivo. The study investigated the relative potencies of angiotensin receptor blockers at inhibiting AT1R signal transducers and lowering aldosterone in vitro and in vivo, though no results were reported in the abstract.
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