γ-MSH, sodium metabolism, and salt-sensitive hypertension
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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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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Anatomy and regulation of the central melanocortin system
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NARRATIVE REVIEW Pathophysiological Mechanisms of Salt-Dependent Hypertension
Rodríguez‐Iturbe, B., Romero, F., & Johnson, R. J. (2007)
(2012) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781849733250-00266
- 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
- Publisher
- American Physiological Society
- 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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