Adrenomedullin inhibits salt appetite

Adrenomedullin (AM) exerts profound natriuretic and vasodilatory effects in conscious animals. This newly discovered hormone also acts in the central nervous system to inhibit water drinking and in the pituitary gland to reduce basal and stimulated ACTH release. We investigated whether the natriuretic action of AM in kidney was matched by a central nervous system action to decrease salt intake. Isotonic hypovolemia induced in male rats by pretreatment with polyethylene glycol potently stimulates both water and salt water (0.3 mol/liter NaCl) drinking. Saline drinking was significantly inhibited when AM was administered into the lateral cerebroventricle before the drinking interval. The effect was dose related (dose range, 44-88 pmol), long lasting (> 5 h), and reversible (resolved at 24 h). When hypovolemic rats were administered antiserum to AM (intracerebroventricular administration) before the drinking interval, a significant 2-fold augmentation of saline drinking was observed. These data suggest that in addition to peripheral actions on cardiovascular and renal function and pituitary actions to inhibit ACTH release, AM may act within the central nervous system to determine fluid and electrolyte balance and, ultimately, blood pressure.