The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Role of Hypothalamic Melanocortin 3/4-Receptors in Mediating Chronic Cardiovascular, Renal, and Metabolic Actions of Leptin
Abstract
The present study examined whether blockade of melanocortin receptors subtypes 3 and 4 (MC3/4-R) inhibits chronic cardiovascular and dietary responses to leptin infusion. A cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic intracerebroventricular (ICV) infusion via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and IV infusions. After a 5-day control period, rats received (1) 0.9% saline vehicle ICV for 12 days plus leptin (1 microg/kg per minute IV, n=5) during the final 7 days; (2) MC3/4-R antagonist SHU-9119 (1 nmol/h ICV) for 12 days plus leptin (1 microg/kg per minute IV, n=6) during the final 7 days; and (3) SHU-9119 (1 nmol/h ICV, n=8) for 12 days. Leptin infusion in vehicle-treated rats caused a small increase in MAP (5+/-1 mm Hg) despite reduced food intake (23+/-1 to 10+/-1 g/d) and decreased body weight (-6%+/-1%). SHU-9119 infusion completely prevented the cardiovascular and dietary actions of leptin, leading to increased food intake (23+/-1 to 49+/-4 g/d) and body weight (+30%+/-2%), markedly decreased HR (-77+/-9 bpm), and caused a decrease in MAP (-6+/-1 mm Hg). Similar results were observed when SHU-9119 was infused alone in vehicle-treated rats. Leptin decreased plasma insulin to 30% of control values, an effect that was also abolished by SHU-9119 treatment, which caused a 5-fold increase in plasma insulin concentration. Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin.
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“In lean normotensive animals, chronic MC4R antagonism caused sustained bradycardia and reduced BP in spite of hyperphagia and rapid weight gain which normally would evoke tachycardia and elevated BP [56].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [56]
In the citing paper
“Blockade of CNS MC4R for 12 consecutive days caused a much greater reduction in BP in SHR than in normotensive Sprague-Dawley or Wistar-Kyoto rats despite causing marked hyperphagia, weight gain, and insulin resistance [42, 56].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [56]
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Cited by
Sorted by citations
Obesity-Associated Hypertension
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The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology
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Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins
Hall, J. E., da Silva, A. A., do Carmo, J. M., Dubinion, J., Hamza, S., Munusamy, S., Smith, G., & Stec, D. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.113175 · Cited by 528
Self-citationObesity, hypertension, and chronic kidney disease
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Self-citationLeptin and Cardiovascular Disease
Koh, K. K., Park, S. M., & Quon, M. J. (2008) · Circulation · doi:10.1161/circulationaha.107.741645 · Cited by 481
Metadata
- Authors
- da Silva, A. A., Kuo, J. J., & Hall, J. E.
- Affiliations
- From the University of Mississippi Medical Center, Jackson.
- University of Mississippi Medical Center (US)
- Venue
- Hypertension
- Published
- 2004-06
- Volume
- 43
- Issue
- 6
- Pages
- 1312-1317
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2134934076
- Cited by
- 117
- References
- 23
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 5
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01-HL-51971, P01HL051971)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- leptin, melanocortin 3/4 receptor, intracerebroventricular infusion, mean arterial pressure, heart rate, dietary intake, body weight, insulin, satiety
- MeSH terms
- Animals, Blood Pressure, Diuresis, Eating, Heart Rate, Hemodynamics, Hypothalamus, Insulin, Kidney, Male, Melanocyte-Stimulating Hormones, Natriuresis, Renin, Satiety Response, Weight Gain, Infusion Pumps, Implantable, Rats, Sprague-Dawley, Leptin, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Rats
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