Novel therapeutic approaches targeting the renin angiotensin system and associated peptides in hypertension and heart failure

Arendse, L. B., Danser, A. H. J., Poglitsch, M., Touyz, R. M. , Burnett Jr, J. C., Llorens-Cortes, C., Ehlers, M. R. and Sturrock, E. D. (2019) Novel therapeutic approaches targeting the renin angiotensin system and associated peptides in hypertension and heart failure. Pharmacological Reviews, 71(4), pp. 539-570. (doi:10.1124/pr.118.017129) (PMID:31537750) (PMCID:PMC6782023)

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Abstract

Despite the success of renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT1R) blockers, current therapies for hypertension and related cardiovascular diseases are still inadequate. Identification of additional components of the RAS and associated vasoactive pathways, as well as new structural and functional insights into established targets, have led to novel therapeutic approaches with the potential to provide improved cardiovascular protection and better blood pressure control and/or reduced adverse side effects. The simultaneous modulation of several neurohumoral mediators in key interconnected blood pressure–regulating pathways has been an attractive approach to improve treatment efficacy, and several novel approaches involve combination therapy or dual-acting agents. In addition, increased understanding of the complexity of the RAS has led to novel approaches aimed at upregulating the ACE2/angiotensin-(1-7)/Mas axis to counter-regulate the harmful effects of the ACE/angiotensin II/angiotensin III/AT1R axis. These advances have opened new avenues for the development of novel drugs targeting the RAS to better treat hypertension and heart failure. Here we focus on new therapies in preclinical and early clinical stages of development, including novel small molecule inhibitors and receptor agonists/antagonists, less conventional strategies such as gene therapy to suppress angiotensinogen at the RNA level, recombinant ACE2 protein, and novel bispecific designer peptides.

Item Type:Articles
Additional Information:This research was additionally supported by British Heart Foundation (CH/4/29762) to RMT, the National Institutes of Health (RO1 HL36634 and RO1 HL134668) to JCB, and the South African National Research Foundation (CPRR160331161352, EQ160511164723) to EDS.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Arendse, L. B., Danser, A. H. J., Poglitsch, M., Touyz, R. M., Burnett Jr, J. C., Llorens-Cortes, C., Ehlers, M. R., and Sturrock, E. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pharmacological Reviews
Publisher:American Society for Pharmacology and Experimental Therapeutics
ISSN:0031-6997
ISSN (Online):1521-0081
Published Online:18 September 2019
Copyright Holders:Copyright © 2019 by The Authors
First Published:First published in Pharmacological Reviews 71(4):539-570
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607382Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)RG/13/7/30099RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES