title: A possible relationship between brain-derived adrenomedullin and oxytocin in the regulation of sodium balance.
abstract: Exaggerated thirst and salt appetite occurs when endogenous, brain-derived adrenomedullin (AM) production is compromised. In addition, the arginine vasopressin (AVP) response to hypovolemia is compromised. We hypothesized that AM acts in the hypothalamus to control oxytocin (OT) release and that the inhibitory action of AM on salt appetite is mediated via its effects on OT release in the rat. When plasma tonicity was elevated with sodium, ribozyme-induced compromise of central AM production significantly blunted the release of OT into plasma. OT responses to elevation of plasma osmolality without concomitant change in plasma sodium levels were not altered by compromise of AM production. Thus, brain-derived AM controls OT release in response to altered plasma sodium levels. Furthermore, central AM-induced inhibition of NaCl intake can be reversed by pretreatment with an OT antagonist, and the increase in NaCl appetite seen following ribozyme compromise of central AM can be attenuated with central OT administration. These data support the hypothesis that endogenous, brain-derived AM is an essential participant in the hypothalamic response to hypernatremia via its actions on OT-expressing neurons. Together with our previous reports of the effects of AM on AVP secretion and ingestive behaviors, our results suggest that endogenous AM is a physiologically relevant regulator of the endocrine and behavioral mechanisms that maintain fluid and electrolyte homeostasis.
authors.affiliation: Department of Pharmacological and Physiological Science, St Louis University School of Medicine, St Louis, Missouri 63104, USA.
authors.forename: Meghan M
authors.initials: MM
authors.lastname: White
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D053607:Adrenomedullin / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001921:Brain / Q000502:physiology*; D008297:Male; D010121:Oxytocin / Q000097:blood / Q000502:physiology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D016337:RNA, Catalytic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage
chemical_list: D016337:RNA, Catalytic; D012982:Sodium, Dietary; D001127:Arginine Vasopressin; D053607:Adrenomedullin; D011092:Polyethylene Glycols; D010121:Oxytocin; D012964:Sodium