Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin
Open accessAbstract
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.
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The blood pressure-increasing effects of neuronostatin and nesfatin 1 were diminished by MC4R blockade.
“The BP-increasing effects of the hormones neuronostatin and nesfatin 1, which are elevated in obesity, were diminished203,204, and hypertension induced by inhibition of NO synthesis was attenuated by MC4R blockade205.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [204]
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Obesity, kidney dysfunction and hypertension: mechanistic links
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- Authors
- Yosten, G. L. C., & Samson, W. K.
- Affiliations
- Saint Louis University (US)
- Corresponding author
- Yosten, Gina L. C.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2014-05-15
- Volume
- 306
- Issue
- 10
- Pages
- R722-R727
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC4025068
- OpenAlex
- W2134216515
- Cited by
- 48
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 6
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (R01HL066023, HL066023)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- nesfatin-1, central hypertension, melanocortin system, corticotropin-releasing factor, oxytocin, alpha-melanocyte-stimulating hormone, mean arterial pressure, neural circuits, food intake regulation
- MeSH terms
- Nucleobindins, alpha-MSH, Animals, Blood Pressure, Calcium-Binding Proteins, Corticotropin-Releasing Hormone, Disease Models, Animal, DNA-Binding Proteins, Hormones, Hypertension, Male, Melanocyte-Stimulating Hormones, Nerve Net, Nerve Tissue Proteins, Oxytocin, Peptide Fragments, Peptides, Cyclic, Vasotocin, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Receptors, Oxytocin, Rats, Melanocortins
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