title: Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system.
abstract: Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation.
authors.affiliation: *División de Enfermedades Cardiovasculares, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Ocaranza
authors.forename: Luis
authors.initials: L
authors.lastname: Michea
authors.affiliation: §Advanced Center for Chronic Diseases (ACCDiS), Centro Estudios Moleculares de la Celula (CMEC), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.affiliation: ∥Departamento de Endocrinología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lagos
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.affiliation: *División de Enfermedades Cardiovasculares, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Jalil
mesh_terms: D000803:Angiotensin I / Q000627:therapeutic use*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000627:therapeutic use*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D044139:Receptor, Angiotensin, Type 2; C506331:angiotensin I (1-9); D000803:Angiotensin I