Document Detail

Microinjections of alpha-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia.
MedLine Citation:
PMID:  19297540     Owner:  NLM     Status:  MEDLINE    
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.
Vineet C Chitravanshi; Suresh Bhatt; Hreday N Sapru
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-18
Journal Detail:
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:
Created Date:  2009-04-28     Completed Date:  2009-06-25     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1402-11     Citation Subset:  IM    
Department of Neurological Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, N.J. 07103, USA.
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MeSH Terms
Baroreflex / drug effects,  physiology
Bradycardia / chemically induced*,  physiopathology
Dose-Response Relationship, Drug
Heart Rate / drug effects,  physiology
Medulla Oblongata / drug effects,  physiology*
Models, Animal
Neurons / drug effects,  metabolism
RNA, Messenger / metabolism
Rats, Wistar
Receptor, Melanocortin, Type 4 / antagonists & inhibitors,  metabolism
Vagus Nerve / physiology*
alpha-MSH / administration & dosage,  adverse effects*,  pharmacology
Grant Support
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, Melanocortin, Type 4; 581-05-5/alpha-MSH

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