Natriuretic peptides differentially modulate endocrine and behavioral stress responses in preclinical and human studies. While atrial natriuretic peptide inhibits the hypothalamic-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.
