Hypothalamic Melanocortin Receptors and Chronic Regulation of Arterial Pressure and Renal Function
Open accessAbstract
This study examined control of cardiovascular and renal function during chronic melanocortin-3/4 receptor (MC3/4-R) activation or inhibition. Arterial and venous catheters were implanted in Sprague-Dawley rats for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and for intravenous infusions, and the lateral ventricle was cannulated for chronic intracerebroventricular (ICV) infusions. In experiment 1, after a 5-day control period, rats were administered the MC3/4-R agonist MTII (n=7, 10 ng/h ICV) or 0.9% saline (n=6, ICV) for 14 days, followed by a 5-day recovery period. In experiment 2, after a 5-day control period, rats were administered the MC3/4-R antagonist SHU-9119 (n=7, 1 nmol/h ICV) or 0.9% saline vehicle (n=7, ICV), or pair-fed during SHU-9119 infusion (n=5, 1 nmol/h ICV) for 12 days, followed by a 5-day recovery period. MC4-R activation transiently decreased food intake from 23±1 to 10±2 g/d. Despite the hypophagia, MC3/4-R activation increased MAP by 7±1 mm Hg. MC3/4-R inhibition for 12 days increased food intake from 21±1 to 35±4 g/d, decreased HR by 53±11 bpm, and caused no change in MAP despite the marked weight gain. In rats that were pair-fed to prevent increased food intake, MC3/4-R inhibition further decreased HR (−87±9 bpm), whereas MAP was unchanged. Thus, chronic hypothalamic MC3/4-R activation raises arterial pressure despite decreased food intake, whereas MC3/4-R inhibition causes marked weight gain without raising arterial pressure. These observations are consistent with the hypothesis that an intact hypothalamic MC3/4-R may be necessary for excess weight gain to raise arterial pressure.
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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 [195]
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 [121]
The increase in blood pressure after chronic activation of MC4R is due to increased adrenergic activity.
“The increase in BP after chronic activation of MC4R is completely abolished after α/β-adrenergic blockade suggesting that it is due to increased adrenergic activity [41].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [41]
The brain melanocortin system plays a key role in maintenance of sympathetic nervous system activity and blood pressure in normotensive subjects as well as in non-obese forms of hypertension that have increased sympathetic activity.
“These findings highlight the key role of the brain melanocortin system in maintenance of SNS activity and BP in normotensive subjects as well as in non-obese forms of hypertension that have increased sympathetic activity [41, 42, 57, 58].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [41]
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 [41]
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“A stainless steel cannula (26 gauge, 10 mm long) was also implanted into the brain right lateral ventricle using coordinates previously described.(18) Ten days after recovery from surgery, accuracy of the cannula was examined by determining the dipsogenic response to an acute injection of 100 ng of Ang II.”
MethodSelf-citation
- Authors
- Kuo, J. J., Silva, A. A., & Hall, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- Venue
- Hypertension
- Published
- 2003-03
- Volume
- 41
- Issue
- 3
- Pages
- 768-774
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W1975374003
- Cited by
- 113
- References
- 26
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 2.36
- 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, 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 › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- melanocortin 3/4 receptor, hypothalamus, arterial pressure, renal function, heart rate, dietary intake, weight gain, melanotan II, intracerebroventricular infusion, pair feeding
- MeSH terms
- alpha-MSH, Animals, Blood Pressure, Eating, Heart Rate, Hormones, Hypothalamus, Kidney, Male, Sodium, Time Factors, Urine, Rats, Sprague-Dawley, Receptors, Corticotropin, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Rats
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