title: Microinjections of alpha-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, N.J. 07103, USA.
authors.forename: Vineet C
authors.initials: VC
authors.lastname: Chitravanshi
authors.forename: Suresh
authors.initials: S
authors.lastname: Bhatt
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*; D000521:alpha-MSH / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH