Abstract 19721: ATF6 is Required for ANP Secretion From the Heart

Introduction: Atrial natriuretic peptide (ANP) is a potent depressor hormone synthesized and stored in the heart in secretory granules of atrial myocytes as a biologically inactive precursor, pro-ANP. Hemodynamic stress and neurohormones, such as the α-adrenergic receptor agonist, phenylephrine (PE) stimulate coordinate secretion and proteolytic cleavage of pro-ANP to its bioactive form, ANP, which promotes renal salt excretion and vasodilation restoring blood pressure. Endoplasmic reticulum (ER) protein folding is critical in all endocrine cells, such as the pancreas because insulin synthesis and folding in the ER of pancreatic β-cells is required for secretion of bioactive insulin. As important as atrial ANP is for normal cardiovascular physiology, ER protein folding and the role of the integral transcription factor, ATF6, which is activated in response to ER protein misfolding in the formation and secretion of bioactive ANP has not been previously examined. Hypothesis: ATF6 is required for optimal secr...