Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure
Top Cited Papers
Open Access
- 18 September 2019
- journal article
- review article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Pharmacological Reviews
- Vol. 71 (4), 539-570
- https://doi.org/10.1124/pr.118.017129
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.Keywords
This publication has 347 references indexed in Scilit:
- Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF)European Journal of Heart Failure, 2013
- Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptidesScientific Reports, 2012
- Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE)Current Opinion in Pharmacology, 2011
- Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptideBiochemical Journal, 2011
- Teaching old receptors new tricks: biasing seven-transmembrane receptorsNature Reviews Drug Discovery, 2010
- Soluble Angiotensin-Converting Enzyme 2 in Human Heart Failure: Relation With Myocardial Function and Clinical OutcomesJournal of Cardiac Failure, 2009
- Discovery and Validation of Novel Peptide Agonists for G-protein-coupled ReceptorsPublished by Elsevier BV ,2008
- Detection of Soluble Angiotensin-Converting Enzyme 2 in Heart Failure: Insights Into the Endogenous Counter-Regulatory Pathway of the Renin-Angiotensin-Aldosterone SystemJournal of the American College of Cardiology, 2008
- Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin‐mediated angioedemaBritish Journal of Pharmacology, 2008
- Definitive role for natriuretic peptide receptor-C in mediating the vasorelaxant activity of C-type natriuretic peptide and endothelium-derived hyperpolarising factorCardiovascular Research, 2007