A physiological role for adrenomedullin in rats; a potent hypotensive peptide in the hypothalamo-neurohypophysial system

Adrenomedullin, a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Adrenomedullin immunoreactivity and gene expressio n are found not only in peripheral organs but also in the central nervous s ystem. Adrenomedullin labelled cells were localised in the hypothalamus, in cluding in the paraventricular and supraoptic nuclei, in rats. Abundant adr enomedullin-immunoreactive fibres and varicosities were found in the hypoth alamo-neurohypophysial tract and the internal zone of the median eminence i n colchicine-treated and hypophysectomized rats, whereas in control rats fe w adrenomedullin-labelled fibres were observed. We examined the effects of intracerebroventricular administration of adrenomedullin on neurosecretory cells in the paraventricular and supraoptic nuclei of rats, using immunohis tochemistry for Pos protein and in situ hybridisation histochemistry for c- fos mRNA. Intracerebroventricular administration of adrenomedullin caused a marked induction of Fos-like immunoreactivity in the paraventricular nucle us and the dorsal part of the supraoptic nucleus. In the paraventricular an d supraoptic nuclei, nuclear Fos-like immunoreactivity was predominantly in oxytocin-immunoreactive cells rather than vasopressin-immunoreactive cells . The induction of c-fos mRNA in the paraventricular and supraoptic nuclei was increased in a dose-related manner 30 min after intracerebroventricular administration of adrenomedullin. This induction was reduced by pre-treatm ent with the adrenomedullin receptor antagonist, human adrenomedullin-(22-5 2)-NH2. Intracerebroventricular administration of adrenomedullin also cause d a marked increase in the plasma concentration of oxytocin. Extracellular recordings from magnocellular neurosecretory cells in the paraventricular n ucleus revealed that putative oxytocin-secreting cells were activated by in tracerebroventricular administration of adrenomedullin. These results sugge st that central adrenomedullin preferentially stimulates the secretion of o xytocin by activating hypothalamic oxytocin-secreting cells and may have an important role in salt appetite and body fluid homeostasis in rats.