title: Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin.
abstract: Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri gyosten@slu.edu.
authors.forename: Gina L C
authors.initials: GL
authors.lastname: Yosten
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri.
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D006728:Hormones / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D053486:Melanocortins / Q000502:physiology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000080866:Nucleobindins; D010121:Oxytocin / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000502:physiology; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D014668:Vasotocin / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D006728:Hormones; D053486:Melanocortins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D018045:Receptors, Oxytocin; C528574:astressin-2B; C103272:SHU 9119; D010121:Oxytocin; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone; D014668:Vasotocin
keywords: CRH; central control of blood pressure; melanocortin; nesfatin-1; oxytocin