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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/R1402    most recent 90978.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chitravanshi, V. C. Articles by Sapru, H. N. Search for Related Content PubMed PubMed Citation Articles by Chitravanshi, V. C. Articles by Sapru, H. N.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Microinjections of -melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia

Department of Neurological Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey

Submitted 3 December 2008 ; accepted in final form 12 March 2009

Neurons that immunostain for alpha-melanocyte stimulating hormone (-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 -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 -MSH. Bradycardic responses to -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 -MSH-induced bradycardia. The decreases in HR elicited by -MSH (0.8 mM) were completely blocked by a selective MC4R antagonist. Direct application of -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 -MSH microinjections into the nAmb exert excitatory effects on parasympathetic preganglionic nAmb neurons via MC4Rs, leading to bradycardic responses.

heart rate; melanocortins; melanocortin receptors; vagus