Hypertension: Renin–Angiotensin–Aldosterone System Alterations

te Riet, Luuk; van Esch, Joep H.M.; Roks, Anton J.M.; van den Meiracker, Anton H.; Danser, A.H. Jan

doi:10.1161/circresaha.116.303587

Cited by 706Renin-Angiotensin System StudiesHormonal Regulation and HypertensionBlood Pressure and Hypertension Studies

Hypertension: Renin–Angiotensin–Aldosterone System Alterations

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te Riet, Luuk, van Esch, Joep H.M., Roks, Anton J.M., van den Meiracker, Anton H., Danser, A.H. Jan·2015·Circulation Research

DOI 10.1161/circresaha.116.303587

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Abstract

Blockers of the renin–angiotensin–aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension.

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Authors: te Riet, L., van Esch, J. H. M., Roks, A. J. M., van den Meiracker, A. H., & Danser, A. H. J.
Affiliations: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Erasmus MC (NL)
ORCID: Roks, Anton J.M.
Danser, A.H. Jan
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-03-13
Volume: 116
Issue: 6
Pages: 960-975
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.116.303587
OpenAlex: W2111256272
Cited by: 706
References: 155
Citations by year: 2026: 44 · 2025: 70 · 2024: 73 · 2023: 84 · 2022: 78 · 2021: 69 · 2020: 74 · 2019: 47 · 2018: 51 · 2017: 57 · 2016: 47 · 2015: 10
FWCI: 40.00
Type: journal article
Language: en
Open access: green
pure.eur.nl
Licence: other-oa
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords: hypertension, renin-angiotensin-aldosterone system, RAAS blockade, renin inhibitors, ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, treatment response prediction, resistant hypertension, primary aldosteronism, angiotensin-(1-7), Mas receptor, ACE2, angiotensin III, aminopeptidase A, angiotensin II type 2 receptor
MeSH terms: Aldosterone, Mineralocorticoid Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Animals, Antihypertensive Agents, Clinical Trials as Topic, Drug Interactions, Drug Resistance, Drug Evaluation, Preclinical, Endothelium, Vascular, Female, Humans, Hyperaldosteronism, Hypertension, Ion Channels, Male, Mice, Transgenic, Renin-Angiotensin System, Sex Characteristics, Sex Chromosomes, Gonadal Steroid Hormones, Therapeutic Equivalency, Vasoconstriction, Drugs, Investigational, Mice, Knockout, Angiotensin II Type 1 Receptor Blockers, Mice, Precision Medicine, Molecular Targeted Therapy

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Hypertension: Renin–Angiotensin–Aldosterone System Alterations

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