| Microinjections of alpha-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia. | |
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MedLine Citation:
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PMID: 19297540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Vineet C Chitravanshi; Suresh Bhatt; Hreday N Sapru |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-03-18 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 296 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-28 Completed Date: 2009-06-25 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R1402-11 Citation Subset: IM |
Affiliation:
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Department of Neurological Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, N.J. 07103, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Baroreflex / drug effects, physiology Bradycardia / chemically induced*, physiopathology Dose-Response Relationship, Drug Heart Rate / drug effects, physiology Male Medulla Oblongata / drug effects, physiology* Microinjections Models, Animal Neurons / drug effects, metabolism RNA, Messenger / metabolism Rats Rats, Wistar Receptor, Melanocortin, Type 4 / antagonists & inhibitors, metabolism Vagotomy Vagus Nerve / physiology* alpha-MSH / administration & dosage, adverse effects*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL024347/HL/NHLBI NIH HHS; HL076248/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptor, Melanocortin, Type 4; 581-05-5/alpha-MSH |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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