Lymperopoulos A, Aukszi B. Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy. World J Cardiol 2017; 9(3): 200-206 [PMID: 28400916 DOI: 10.4330/wjc.v9.i3.200]
Corresponding Author of This Article
Anastasios Lymperopoulos, PhD, FAHA, FESC, Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 S. University Dr., HPD (Terry) Bldg/Room 1338, Fort Lauderdale, FL 33328, United States. al806@nova.edu
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Mar 26, 2017; 9(3): 200-206 Published online Mar 26, 2017. doi: 10.4330/wjc.v9.i3.200
Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy
Anastasios Lymperopoulos, Beatrix Aukszi
Anastasios Lymperopoulos, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States
Beatrix Aukszi, Department of Chemistry and Physics, Halmos College of Natural Sciences and Oceanography, Nova Southeastern University, Fort Lauderdale, FL 33328, United States
Author contributions: Aukszi B contributed to the “Implications for AT1R blocker medicinal chemistry” section of the manuscript; Lymperopoulos A contributed to all of the paper.
Conflict-of-interest statement: Both authors declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Anastasios Lymperopoulos, PhD, FAHA, FESC, Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 S. University Dr., HPD (Terry) Bldg/Room 1338, Fort Lauderdale, FL 33328, United States. al806@nova.edu
Telephone: +1-954-2621338 Fax: +1-954-2622278
Received: August 12, 2016 Peer-review started: August 12, 2016 First decision: October 20, 2016 Revised: November 29, 2016 Accepted: December 16, 2016 Article in press: December 19, 2016 Published online: March 26, 2017 Processing time: 226 Days and 16.2 Hours
Core Tip
Core tip: The angiotensin II type 1 receptor (AT1R) endogenously expressed in adrenocortical cells was known for decades to induce aldosterone production via a well-defined Gq protein-mediated signaling pathway. Over the past decade, a number of studies have elucidated another, β-arrestin-1 (βarr1)-dependent signaling cascade, which proceeds in parallel to, and independently of the Gq-mediated one, and also results in aldosterone synthesis and secretion from the adrenal cortex. Importantly, although all of the Food and Drug Administration-approved angiotensin receptor blocker (ARB) drugs (AT1R antagonists) are very effective at blocking the Gq-mediated pathway, as expected, since they were designed to do so (i.e., to block the G protein signaling of the AT1R), they seem to display varying efficacies at blocking this new, βarr1-dependent pathway, which translates into significant variation at aldosterone suppression efficacies. In that context, candesartan and valsartan appear the most effective agents at blocking also the βarr1 pathway emanating from the adrenocortical AT1R, and thus, these two agents may be the best aldosterone suppressors within the ARB drug class.
