Neurons that immunostain for alpha-melanocyte stimulating hormone (α-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 α-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 α-MSH. Bradycardic responses to α-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 α-MSH-induced bradycardia. The decreases in HR elicited by α-MSH (0.8 mM) were completely blocked by a selective MC4R antagonist. Direct application of α-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 α-MSH microinjections into the nAmb exert excitatory effects on parasympathetic preganglionic nAmb neurons via MC4Rs, leading to bradycardic responses.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|State||Published - May 2009|
All Science Journal Classification (ASJC) codes
- Physiology (medical)
- Heart rate
- Melanocortin receptors