Microinjections of α-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia
Open accessAbstract
Neurons that immunostain for alpha-melanocyte stimulating hormone (alpha-MSH) have been identified in the nucleus ambiguus (nAmb). The presence of mRNA for melanocortin type 4 receptors (MC4Rs) has also been reported in this nucleus. On the basis of this information, it was hypothesized that activation of MC4Rs in the nAmb may play a role in the regulation of cardiac function. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (30 nl) of alpha-MSH (0.1, 0.2, 0.4, 0.8, and 1.2 mM) into the nAmb of anesthetized rats elicited decreases in heart rate (HR; 1.3 +/- 0.6, 3 +/- 1, 11 +/- 2, 46.3 +/- 3, and 43.3 +/- 7 bpm, respectively) and no changes in mean arterial pressure (MAP). Maximum decreases in HR were elicited by 0.8 mM concentration of alpha-MSH. Bradycardic responses to alpha-MSH were similar in unanesthetized midcollicular decerebrate rats. Microinjections of artificial cerebrospinal fluid (30 nl) into the nAmb did not elicit a HR response. Bilateral vagotomy completely abolished alpha-MSH-induced bradycardia. The decreases in HR elicited by alpha-MSH (0.8 mM) were completely blocked by a selective MC4R antagonist. Direct application of alpha-MSH on the nAmb neurons increased their firing, which was blocked by prior applications of the MC4R antagonist. Microinjections of the MC4R antagonist into the nAmb did not alter reflex bradycardic responses elicited by intravenous infusions of phenylephrine, suggesting that MC4Rs did not play a role in mediating the parasympathetic component of baroreflex-induced bradycardia. These results indicated that alpha-MSH microinjections into the nAmb exert excitatory effects on parasympathetic preganglionic nAmb neurons via MC4Rs, leading to bradycardic responses.
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α-MSH and γ1-MSH have protective effects in a rat model of transient myocardial infarction followed by reperfusion and in a rat model of permanent coronary artery occlusion.
“For instance, α-MSH and γ1-MSH have protective effects in a model of transient myocardial infarction (MI) followed by reperfusion as well as in a model of permanent coronary artery occlusion in rats [66].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [66]
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Role of the brain melanocortins in blood pressure regulation
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Perez de Lara, C. E., & Hall, J. E. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.003 · Cited by 38 · see citing works
- Authors
- Chitravanshi, V. C., Bhatt, S., & Sapru, H. N.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Rutgers, The State University of New Jersey (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2009-05
- Volume
- 296
- Issue
- 5
- Pages
- R1402-R1411
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC2689839
- OpenAlex
- W2132111461
- Cited by
- 16
- References
- 49
- Citations by year
- 2022: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL076248, R01HL024347, HL024347, R01HL076248)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- alpha-melanocyte-stimulating hormone, nucleus ambiguus, vagal bradycardia, vagotomy, preganglionic neurons, heart rate regulation, parasympathetic preganglionic neurons, melanocortin system, baroreflex bradycardia, phenylephrine
- MeSH terms
- alpha-MSH, Animals, Bradycardia, Dose-Response Relationship, Drug, Heart Rate, Male, Medulla Oblongata, Microinjections, Neurons, RNA, Messenger, Vagotomy, Vagus Nerve, Rats, Wistar, Baroreflex, Models, Animal, Receptor, Melanocortin, Type 4, Rats
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