title: New agents modulating the renin-angiotensin-aldosterone system-Will there be a new therapeutic option?
abstract: The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT1receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT1axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland anna.gromotowicz@umb.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Gromotowicz-Poplawska
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Szoka
authors.affiliation: Department of Pharmaceutical Analysis, Medical University of Bialystok, 15-522 Bialystok, Poland.
authors.forename: Patrycjusz
authors.initials: P
authors.lastname: Kolodziejczyk
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Kramkowski
authors.affiliation: Department of Emergency and Disaster Medicine, Medical University of Bialystok, 15-295 Bialystok, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wojewodzka-Zelezniakowicz
authors.affiliation: Department of Biopharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Chabielska
mesh_terms: D000450:Aldosterone / Q000502:physiology; D000803:Angiotensin I / Q000502:physiology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D000450:Aldosterone; D000803:Angiotensin I; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: Angiotensin converting enzyme 2; Mas receptor; aldosterone synthase inhibitors; angiotensin-(1-7); finerenone; mineralocorticoid receptor coregulators