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Angiotensin‐(1‐7) stimulates high atrial pacing‐induced ANP secretion
Author(s) -
Shah Amin,
Gul Rukhsana,
Yuan Kuichang,
Shan Gao,
Oh Youngbin,
Kim UhHyun,
Kim Suhn Hee
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1040.2
Subject(s) - atrial natriuretic peptide , medicine , endocrinology , angiotensin ii , chemistry , renin–angiotensin system , nitric oxide synthase , angiotensin ii receptor type 1 , receptor , nitric oxide , blood pressure
Angiotensin‐(1‐7) [Ang‐(1‐7)] has many beneficial roles in cardiovascular physiology, counterbalancing Angiotensin II functions. It is considered as one of the theurapeutic agent for cardiovascular diseases in the future. The aim of the present study is to elucidate the modulatory role of Ang‐(1‐7) in atrial natriuretic peptide (ANP) secretion using isolated perfused beating rat atria and cardiac hypertrophied rat model. Ang‐(1‐7) (10 −8 , 10 −7 , and 10 −6 M) increased the ANP secretion and ANP concentration in a dose‐dependent manner at high atrial pacing (6.0 Hz) with an increased cGMP amount. However, Ang‐(1‐7) did not cause any changes in atrial parameters at low atrial pacing (1.2 Hz). An antagonist of Mas receptor or inhibitors of phosphoinositide 3‐kinase (PI3K), protein kinase B (Akt), or nitric oxide synthase pretreatment blocked the increase of high atrial pacing‐induced ANP secretion by Ang‐(1‐7). The inhibition of Na + /H + exchanger‐1 (NHE‐1) and calcium/calmodulin‐dependent kinase II (CaMKII) showed the similar result. Ang‐(1‐7) did not show any changes in intracellular calcium concentration in quiescent atrial myocytes. However, Ang‐(1‐7) attenuated an increase of intracellular calcium concentration induced by angiotensin II. Intravenous infusion of Ang‐(1‐7) increased the plasma concentration of ANP by 2‐fold without changes in blood pressure and heart rate in isoproterenol‐treated rats but not in control rats. Ang‐(1‐7) attenuated cardiac hypertrophy induced by isoproterenol. These results suggest that Ang‐(1‐7) increased the ANP secretion at high atrial pacing via Mas/PI3K/Akt pathway and the activation of NHE‐1 and CaMKII. Supported by the KOSEF (R13‐2008‐005‐‐0).