Atrial secretion of ANP is suppressed in renovascular hypertension: Shifting of ANP secretion from atria to the left ventricle

Abstract

The change of the secretion of atrial natriuretic peptide (ANP) from the atria is to be defined in hypertension accompanied by ventricular hypertrophy and increased synthesis of ANP. 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. Expressions of ANP, natriuretic peptide receptor (NPR)-C, components of the renin-angiotensin system (RAS) and muscarinic signaling pathway were measured in cardiac tissues. Basal levels of ANP secretion and the ACh-and stretch-induced activation of ANP secretion were suppressed in the atria from hypertensive compared to normotensive rats. ACh increased ANP secretion via M2 mAChR-KACh channel signaling. In hypertensive rats, ANP concentration increased in the left but decreased in the right ventricle. The atrial concentration of ANP was not changed in the hypertensive compared to normotensive rats. ANP mRNA expression accentuated in the left ventricle but suppressed in the other cardiac chambers of the hypertensive rats. NPR-C expression was inversely related to the ANP mRNA. Angiotensin II subtype 1 (AT1) receptor expression was accentuated in the cardiac chambers from hypertensive rats compared to normotensive rats, while AT2 receptor, M2 muscarinic receptor and Kir3.4 channel suppressed. AT1 receptor blockade with losartan reversed the change observed in the 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, AT1 receptor, and M2 muscarinic signaling pathway.