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Cited by 25Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyCardiovascular, Neuropeptides, and Oxidative Stress Research

Cardiovascular effects of melanocortins

Open access
Humphreys, Michael H., Ni, Xi-Ping, Pearce, David·2011·European Journal of Pharmacology
DOI 10.1016/j.ejphar.2010.10.102PMC PMC3086937
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Abstract

Melanocortins (MSH's) are three structurally related peptides derived from proopiomelanocortin. They regulate several physiologic functions including energy metabolism, appetite, and inflammation. Recent work in rodents has also identified important effects of MSH's, particularly γ-MSH, on sodium metabolism and blood pressure regulation. Normal rats and mice respond to a high sodium diet with an increase in the plasma concentration of γ-MSH, and remain normotensive, while those with genetic or pharmacologic γ-MSH deficiency become hypertensive on a high sodium diet. This hypertension is corrected by exogenous administration of the peptide. Mice lacking the γ-MSH receptor (the melanocortin 3 receptor, Mc3r) also become hypertensive on a high sodium diet but remain so when administered γ-MSH, and infusions of physiologic levels of the peptide stimulate urinary sodium excretion in normal rats and mice, but not in mice with deletion of Mc3r. The salt-sensitive hypertension in rodents with impaired γ-MSH signaling appears due to stimulation of noradrenergic activity, since plasma noradrenaline is increased and the hypertension is rapidly corrected with infusion of the α-adrenoceptor antagonist phentolamine. In contrast to the antihypertensive property of physiologic levels of γ-MSH, intravenous or intracerebroventricular injections of high levels of the peptide raise blood pressure. This occurs in mice lacking Mc3r, indicating an interaction with some other central receptor. Finally, the salt-sensitive hypertension in rodents with disruption of γ-MSH signaling is accompanied by insulin resistance, an observation which offers a new window into the study of the association of salt-sensitive hypertension with insulin resistance and type II diabetes.

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  • γ-MSH has pro-hypertensive as well as antihypertensive actions.

    “Previous studies have suggested that γ-MSH has pro-hypertensive as well as antihypertensive actions [15].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [15]

  • Injections of γ-MSH intravenously or intracerebroventricularly raise blood pressure and heart rate.

    “Injections of γ-MSH (i.v. or ICV) have been reported to raise BP and HR, although injections into the NTS lower BP and HR [15].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [15]

  • γ-MSH-induced natriuresis appears to be mediated primarily by activation of MC3R and subsequent stimulation of cAMP production in the kidney.

    “Although the physiological significance of γ-MSH-induced natriuresis has not been fully elucidated, the effect appears to be mediated primarily by activation of MC3R and subsequent stimulation of cAMP production in the kidney [15].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [15]

  • Injections of γ-MSH into the nucleus tractus solitarius lower blood pressure and heart rate.

    “Injections of γ-MSH (i.v. or ICV) have been reported to raise BP and HR, although injections into the NTS lower BP and HR [15].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [15]

  • γ-MSH has natriuretic effects when infused directly into the renal artery.

    “Several studies have demonstrated that γ-MSH also has natriuretic effects when infused directly into the renal artery [15, 20].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [15]

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Authors
Humphreys, M. H., Ni, X.-P., & Pearce, D.
Affiliations
San Francisco General Hospital (US)
Corresponding author
Humphreys, Michael H.
ORCID
Pearce, David
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2011-06
Volume
660
Issue
1
Pages
43-52
ISSN
0014-2999 (ISSN-L)
DOI
10.1016/j.ejphar.2010.10.102
PMC
PMC3086937
OpenAlex
W2090422970
Cited by
25
References
96
Citations by year
2026: 2 · 2023: 1 · 2021: 2 · 2019: 2 · 2018: 5 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 1
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL068871, HL 68871)
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
melanocortin peptides, gamma-MSH, proopiomelanocortin, melanocortin 3 receptor, salt-sensitive hypertension, high-salt diet, sodium metabolism, blood pressure regulation, sodium excretion, norepinephrine, alpha-adrenoceptor antagonism, phentolamine, insulin resistance, type 2 diabetes, cardiovascular effects
MeSH terms
Animals, Blood Pressure, Cardiovascular System, Glucose, Humans, Signal Transduction, gamma-MSH, Melanocortins

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