title: Brain-derived adrenomedullin controls blood volume through the regulation of arginine vasopressin production and release.
abstract: Central nervous system-derived adrenomedullin (AM) has been shown to be a physiological regulator of thirst. Administration of AM into the lateral ventricle of the brain attenuated water intake, whereas a decrease in endogenous AM, induced by an AM-specific ribozyme, led to exaggerated water intake. We hypothesized that central AM may control fluid homeostasis, in part by regulating plasma arginine vasopressin (AVP) levels. To test this hypothesis, AM or a ribozyme specific to AM was administered intracerebroventricularly, and alterations in plasma AVP concentrations were examined under basal and stimulated (hypovolemic) conditions. Additionally, we examined changes in blood volume, kidney function, and plasma electrolyte and protein levels, as well as changes in plasma aldosterone concentrations. Intracerebroventricular administration of AM increased plasma AVP levels, whereas AM ribozyme treatment led to decreased plasma AVP levels under stimulated conditions. During hypovolemic challenges, AM ribozyme treatment led to an increased loss of plasma volume compared with control animals. Although overall plasma osmolality did not differ between treatment groups during hypovolemia, aldosterone levels were significantly higher and, consequently, plasma potassium concentrations were lower in AM ribozyme-treated rats than in controls. These data suggest that brain-derived AM is a physiological regulator of vasopressin secretion and, thereby, fluid homeostasis.
authors.affiliation: Dept. of Pharmacological and Physiological Science, Saint Louis Univ., 1402 South Grand Blvd., St. Louis, MO 63104, USA. taylormm@slu.edu
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Taylor
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Baker
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D053607:Adrenomedullin; D000450:Aldosterone / Q000502:physiology; D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis / Q000378:metabolism*; D001810:Blood Volume / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008297:Male; D010455:Peptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016337:RNA, Catalytic; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010455:Peptides; D016337:RNA, Catalytic; D001127:Arginine Vasopressin; D053607:Adrenomedullin; D000450:Aldosterone; D003404:Creatinine