Abstract
Natriuretic peptides differentially modulate endocrine and behavioral stress responses in preclinical and human studies. While atrial natriuretic peptide inhibits thehypothalamic–pituitary–adrenocortical axis, C-type natriuretic peptide exerts stimulatory activity. In rodents, atrial natriuretic peptide reduces anxiety, whereas C-type natriuretic peptide has anxiogenic effects (mediated via corticotropin-releasing hormone). Patients with panic disorder show lower basal ANP plasma levels but a more pronounced release during experimentally induced panic attacks compared with controls. This could explain the absent pituitary–adrenocortical activation during panic anxiety and its paroxysmal nature. Furthermore, the effects of the panicogen cholecystokinin–tetrapeptide are attenuated by ANP pretreatment in panic patients, while C-type natriuretic peptide demonstrates anxiogenic action in healthy humans. Atrial natriuretic peptide agonists and C-type natriuretic peptide antagonists may have potential as a new class of antipanic and anxiolytic psychotherapeutic medication.