title: Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor.
abstract: Angiotensin-(1-5) [Ang-(1-5)], which is a metabolite of Angiotensin-(1-7) [Ang-(1-7)] catalyzed by angiotensin-converting enzyme (ACE), is a pentapeptide of the renin-angiotensin system (RAS). It has been reported that Ang-(1-7) and Ang-(1-9) stimulate the secretion of atrial natriuretic peptide (ANP) via Mas receptor (Mas R) and Ang II type 2 receptor (AT2R), respectively. However, it still remains unknown whether Ang-(1-5) has a similar function to Ang-(1-7). We investigated the effect of Ang-(1-5) on ANP secretion and to define its signaling pathway using isolated perfused beating rat atria. Ang-(1-5) (0.3, 3, 10μM) stimulated high pacing frequency-induced ANP secretion in a dose-dependent manner. Ang-(1-5)-induced ANP secretion (3μM) was attenuated by the pretreatment with an antagonist of Mas R (A-779) but not by an antagonist of AT1R (losartan) or AT2R (PD123,319). An inhibitor for phosphatidylinositol 3-kinase (PI3K; wortmannin), protein kinase B (Akt; API-2), or nitric oxide synthase (NOS; L-NAME) also attenuated the augmentation of ANP secretion induced by Ang-(1-5). Ang-(1-5)-induced ANP secretion was markedly attenuated in isoproterenol-treated hypertrophied atria. The secretagogue effect of Ang-(1-5) on ANP secretion was similar to those induced by Ang-(1-9) and Ang-(1-7). These results suggest that Ang-(1-5) is an active mediator of renin-angiotensin system to stimulate ANP secretion via Mas R and PI3K-Akt-NOS pathway.
authors.affiliation: Department of Physiology, Research Institute for Endocrine Sciences Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Yanbian University, China.
authors.forename: Kuichang
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Research Institute for Endocrine Sciences Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Hoang Thi Ai
authors.initials: HT
authors.lastname: Phuong
authors.affiliation: Department of Physiology, Research Institute for Endocrine Sciences Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Byung Mun
authors.initials: BM
authors.lastname: Park
authors.affiliation: Department of Physiology, Research Institute for Endocrine Sciences Chonbuk National University Medical School, Jeonju, Republic of Korea. Electronic address: shkim@chonbuk.ac.kr.
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System; D015398:Signal Transduction
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; C000625519:angiotensin II (1-5); D000804:Angiotensin II; D009320:Atrial Natriuretic Factor
keywords: Angiotensin-(1-5); Angiotensin-(1-7); Atrial natriuretic peptide; Hypertrophy; Isoproterenol; Receptor