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.
Recommended Citation
G. L. Yosten and W. K. Samson, "Neural Circuitry Underlying the Central Hypertensive Action of Nesfatin-1: Melanocortins, Corticotropin-releasing Hormone, and Oxytocin," American Journal of Physiology Regulatory Integrative and Comparative Physiology, vol. 306, no. 10, pp. R722 - R727, American Physiological Society, May 2014.
The definitive version is available at https://doi.org/10.1152/ajpregu.00396.2013
Department(s)
Biological Sciences
Publication Status
Open Access
Keywords and Phrases
Central control of blood pressure; CRH; Melanocortin; Nesfatin-1; Oxytocin
International Standard Serial Number (ISSN)
1522-1490; 0363-6119
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 American Physiological Society, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
15 May 2014
PubMed ID
24598461
Comments
National Heart, Lung, and Blood Institute, Grant 10GRNT4470043