Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor

作者：Yu, Lamei; Yuan, Kuichang; Hoang Thi Ai Phuong; Park, Byung Mun; Kim, Suhn Hee^*

来源：Peptides, 2016, 86: 33-41.

DOI：10.1016/j.peptides.2016.09.009

• Atrial natriuretic peptide
• Angiotensin-(1-5)
• Angiotensin-(1-7)
• Receptor
• Isoproterenol
• Hypertrophy

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 (AT(2)R), 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, 10 mu M) stimulated high pacing frequency-induced ANP secretion in a dose-dependent manner. Ang-(15)-induced ANP secretion (3 mu M) was attenuated by the pretreatment with an antagonist of Mas R (A-779) but not by an antagonist of AT(1)R (losartan) or AT(2)R (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.

• 出版日期2016-12
• 单位延边大学