Atrial Natriuretic Peptide, the Hypothalamic–Pituitary–Adrenal Axis, and Panic Attacks

Abstract

Abstract Natriuretic peptides differentially modulate endocrine and behavioral stress responses in animal and human studies. Especially atrial natriuretic peptide inhibits the hypothalamic–pituitary–adrenocortical axis and exerts anxiolytic actions, while C-type natriuretic peptide activates the stress system and displays anxiogenic effects mediated by corticotropin-releasing hormone. Brain natriuretic peptide, although originally purified from pig brain, does not play a major role regarding behavioral effects of natriuretic peptides. Patients with panic disorder show lower basal atrial natriuretic peptide plasma levels but increased release during experimentally induced panic attacks compared with controls in various panic models. The observed absent pituitary–adrenocortical activation during panic anxiety and its paroxysmal nature could be rooted here. Furthermore, the panicogen effects of cholecystokinin tetrapeptide are attenuated by atrial natriuretic peptide pretreatment in panic patients, while C-type natriuretic peptide demonstrates anxiogenic action in healthy humans. Compounds interacting with the natriuretic peptide system may have potential as a new class of antipanic and anxiolytic psychotherapeutic medication.