Adrenomedullin and the control of fluid and electrolyte homeostasis

Two potent hypotensive peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP), are encoded by the adrenomedullin gene. AM stimulates nitric oxide production by endothelial cells, whereas PAMP acts presynaptically to inhibit adrenergic nerves that innervate blood vessels. Complementary, but mechanistically unique, actions also occur in the anterior pituitary gland where both peptides inhibit adrenocorticotropin release. In the adrenal gland both AM and PAMP inhibit potassium and angiotensin II-stimulated aldosterone secretion. Natriuretic and diuretic actions of AM reflect unique actions of the peptide on renal blood flow and tubular function. In the brain AM inhibits water intake and, in a physiologically relevant manner, salt appetite. Both AM and PAMP act in the brain to elevate sympathetic tone, effects that mirror the positive inotropic action of AM in the heart. Cardioprotective actions in the brain and heart may be important counter-regulatory actions that buffer the extreme hypotensive actions of the peptides when released in sepsis. Thus the biologic actions of the proadrenomedullin-derived peptides seem well coordinated to contribute to the physiologic regulation of volume and electrolyte homeostasis.