Role of Adrenergic Activity in Pressor Responses to Chronic Melanocortin Receptor Activation
Open accessAbstract
Acute studies have shown that MC3/4-R stimulation increases sympathetic activity, but the role of adrenergic activation in mediating the cardiovascular and renal responses to chronic melanocortin 3- and 4-receptor (MC3/4-R) activation is unknown. The present study tested whether chronic MC3/4-R activation raises blood pressure and whether these changes are attenuated by α 1 +β-adrenergic blockade. Rats were instrumented with an intracerebroventricular (ICV) cannula and arterial and venous catheters for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 hours per day, and intravenous infusions. After control measurements, rats were intravenously infused with either saline vehicle (n=7) or α 1 + β-adrenergic antagonists (n=6, terazosin+propranolol, 10 mg/kg per day each) for 21 days. Five days after starting the vehicle or adrenergic blockade, the MC3/4-R agonist, MTII (10 ng/h), was infused ICV for 11 days followed by a 5-day recovery period. Another group of rats was infused with the adrenergic antagonists for 21 days but received the saline vehicle ICV for 11 days (n=7). MC3/4-R activation decreased food intake from 21±1 to 8±2 g/d by day 3 of MC3/4-R activation, and increased MAP and HR by an average of 8±2 mm Hg and 9±5 bpm, respectively. Adrenergic blockade did not alter the MC3/4-R-mediated decrease in food intake but abolished the increases in MAP and HR (1±2 mm Hg and −12±5 bpm, respectively, compared with control). ICV vehicle infusion during adrenergic blockade did not alter food intake or MAP. Glomerular filtration rate was unchanged in both the vehicle-infused and adrenergic blocked rats during MC3/4-R activation. These results indicate that the chronic actions of MC3/4-R activation on MAP and HR are mediated by adrenergic activation.
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In rats, pharmacological activation of MC4R reduced food intake and body weight but increased blood pressure; these effects were abolished by α/β-adrenergic blockade.
“In rats, pharmacological activation of MC4R reduced food intake and body weight but increased BP; these effects were abolished by α/β-adrenergic blockade195,196.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [196]
Chronic pharmacological activation of CNS MC4R in rats increases BP while reducing appetite and body weight, and the rise in BP is abolished after α/β-adrenergic blockade.
“Chronic pharmacological activation of CNS MC4R in rats increases BP while reducing appetite and body weight121. The rise in BP after chronic activation of MC4R is abolished after α/β-adrenergic blockade indicating that it is due to increased adrenergic activity122.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [122]
Chronic pharmacological activation of central nervous system MC4R in rats increased blood pressure while reducing appetite and body weight.
“Chronic pharmacological activation of CNS MC4R in rats increased BP while reducing appetite and body weight [40].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [40]
Chronic ICV administration of MT-II, a non-selective MC3/4R agonist, raised blood pressure in rodents due to adrenergic activation.
“Our early studies demonstrated, for example, that chronic ICV administration of MT-II, a non-selective MC3/4R agonist, raised BP in rodents due to adrenergic activation [40, 41].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [40]
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“For instance, acute ICV injections of MC4R agonists raise SNA to several tissues, including the kidneys, and combined α- and β-adrenergic receptors blockade completely prevented the hypertension caused by chronic central MC3/4R stimulation using the synthetic agonist MTII.(20) A role for modulation of SNA by CNS MC3/4…”
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Self-citation
- Authors
- Kuo, J. J., da Silva, A. A., Tallam, L. S., & Hall, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
- Venue
- Hypertension
- Published
- 2004-02
- Volume
- 43
- Issue
- 2
- Pages
- 370-375
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2092553459
- Cited by
- 68
- References
- 25
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 4
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Heart, Lung, and Blood Institute (PO1HL-51971, 51971, P01-HL-51971, P01HL051971)
- 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 3/4 receptor, adrenergic blockade, terazosin, propranolol, blood pressure, heart rate, dietary intake, glomerular filtration rate, pressor response, intracerebroventricular infusion, sympathetic activity
- MeSH terms
- alpha-MSH, Animals, Blood Pressure, Eating, Heart Rate, Kidney, Male, Rats, Sprague-Dawley, Adrenergic Antagonists, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Rats
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