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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-09-0284v1 203/2/253    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by White, M. M Articles by Samson, W. K PubMed PubMed Citation Articles by White, M. M Articles by Samson, W. K

Department of Pharmacological and Physiological Science, St Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, Missouri 63104, USA

(Correspondence should be addressed to W K Samson; Email: samsonwk{at}slu.edu)

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.