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To identify the change of the secretion and mechanisms involved, experiments were performed in isolated perfused beating atria from sham-operated normotensive and renovascular hypertensive rats. Expression of ANP, natriuretic peptide receptor (NPR)-C, components of the renin-angiotensin system, and muscarinic signaling pathway was measured in cardiac tissues. Basal levels of ANP secretion and acetylcholine (ACh)- and stretch-induced activation of ANP secretion were suppressed in the atria from hypertensive compared with normotensive rats. ACh increased ANP secretion via M<jats:sub>2<\/jats:sub>muscarinic ACh receptor-ACh-sensitive K<jats:sup>+<\/jats:sup>channel signaling. In hypertensive rats, ANP concentration increased in the left ventricle but decreased in the right ventricle. The atrial concentration of ANP was not changed in hypertensive compared with normotensive rats. ANP mRNA expression was accentuated in the left ventricle but suppressed in the other cardiac chambers in the hearts of hypertensive rats. NPR-C expression was inversely related to ANP mRNA levels. Angiotensin II type 1 receptor (AT<jats:sub>1<\/jats:sub>R) expression was accentuated in the cardiac chambers from hypertensive rats compared with normotensive rats, whereas angiotensin II type 2 receptor, M<jats:sub>2<\/jats:sub>muscarinic receptor, and Kir3.4 channels were suppressed. AT<jats:sub>1<\/jats:sub>R blockade with losartan reversed the change observed in hypertensive rats. The present findings indicate that renovascular hypertension shifts the major site of ANP secretion and synthesis from the atria to the left ventricle through modulation of the expression of ANP, NPR-C, AT<jats:sub>1<\/jats:sub>R, and the M<jats:sub>2<\/jats:sub>muscarinic signaling pathway.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Renovascular hypertension suppresses the atrial secretion of ANP and shifts the major site of the regulation of ANP secretion and synthesis from atria to the hypertrophied left ventricle possibly via modulation of the expression of ANP, natriuretic peptide receptor-C, angiotensin II subtype 1 receptor, and M2 muscarinic signaling pathway.<\/jats:p>","DOI":"10.1152\/ajpheart.00612.2017","type":"journal-article","created":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T19:02:57Z","timestamp":1530903777000},"page":"H590-H601","source":"Crossref","is-referenced-by-count":9,"title":["Atrial secretion of ANP is suppressed in renovascular hypertension: shifting of 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