Cited by 51Neuropeptides and Animal PhysiologyRenin-Angiotensin System StudiesCardiovascular, Neuropeptides, and Oxidative Stress Research

γ-MSH, sodium metabolism, and salt-sensitive hypertension

Humphreys, Michael H.·2004·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

Abstract

Alpha-, beta-, and gamma-melanocyte stimulating hormones (MSHs) are melanotropin peptides that are derived from the ACTH/beta-endorphin prohormone proopiomelanocortin (POMC). They have been highly conserved through evolutionary development, although their functions in mammals have remained obscure. The identification in the last decade of a family of five membrane-spanning melanocortin receptors (MC-Rs), for which the melanotropins are the natural ligands, has permitted the characterization of a number of important actions of these peptides, although the physiological function(s) of gamma-MSH have remained elusive. Much evidence indicates that gamma-MSH stimulates sympathetic outflow and raises blood pressure through a central mechanism. However, this review focuses on newer cardiovascular and renal actions of the peptide, acting in most cases through the MC3-R. In rodents, a high-sodium diet (HSD) increases the pituitary abundance of POMC mRNA and of gamma-MSH content and results in a doubling of plasma gamma-MSH concentration. The peptide is natriuretic and acts through renal MC3-Rs, which are also upregulated by the HSD. Thus the system appears designed to participate in the integrated response to dietary sodium excess. Genetic or pharmacologic induction of gamma-MSH deficiency results in marked salt-sensitive hypertension that is corrected by the administration of the peptide, probably through a central site of action. Deletion of the MC3-R also produces salt-sensitive hypertension, which, however, is not corrected by infusion of the hormone. These observations in aggregate suggest the operation of a hormonal system important in blood pressure control and in the regulation of sodium excretion. The relationship of these two actions to each other and the significance of this system in humans are important questions for future research.

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Crossref · 10.1152/ajpregu.00365.2003

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  • 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 [20]

  • Physiological activation of the γ-MSH-MC3R pathway by high sodium intake may protect against the development of salt-sensitive hypertension.

    “These observations suggest that physiological activation of the γ-MSH–MC3R pathway by high sodium intake may protect against the development of salt-sensitive hypertension [20].”

    From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [20]

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Authors
Humphreys, M. H.
Affiliations
San Francisco General Hospital (US)
Corresponding author
Humphreys, Michael H.
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Published
2004-03
Volume
286
Issue
3
Pages
R417-R430
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
OpenAlex
W2152645306
Cited by
51
References
132
Citations by year
2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2013: 2 · 2012: 6
FWCI
0.55
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01-HL-68871, R01HL068871)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
Keywords
gamma-MSH, melanocortin 3 receptor, salt-sensitive hypertension, sodium metabolism, sodium excretion, high-salt diet, proopiomelanocortin, blood pressure regulation, renal sodium excretion, sympathetic nervous system
MeSH terms
Animals, Hemodynamics, Humans, Hypertension, Natriuresis, Nephrectomy, Pro-Opiomelanocortin, Receptors, Pituitary Hormone, Sodium, Sodium Chloride, Structure-Activity Relationship, gamma-MSH

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