Microinjections of alpha‐MSH into the nucleus ambiguus of the rat elicit vagally mediated bradycardia

Abstract

Alpha melanocyte stimulating hormone (alpha‐MSH) is one of the pro‐opiomelanocortin‐related end products. Alpha‐MSH containing neurons are found in different hypothalamic nuclei and the nucleus tractus solitarius. Since these brain regions are known to project to the nucleus ambiguus (NA), it was hypothesized that alpha‐MSH may elicit cardiac effects in the NA. Experiments were done on urethane‐anesthetized, artificially ventilated, adult, male, Wistar rats. NA was identified by microinjections (30 nl) of L‐glutamate; bradycardic responses with no changes in blood pressure (BP) were elicited. Unilateral microinjections (30 nl) of different concentrations (0.1–1.6 mM) of alpha‐MSH into the NA elicited bradycardic responses (7–44 beats/min) with no changes in BP. The bradycardic responses to maximally effective concentration of alpha‐MSH (0.8 mM) lasted for 10 min and were blocked by prior microinjections of a specific MC4 receptor antagonist. MC4 receptor antagonist by itself elicited a small decrease in heart rate. Bilateral vagotomy abolished the bradycardic responses to microinjections of alpha‐MSH into the NA. These results indicate that: 1) microinjections of alpha‐MSH into the NA elicit bradycardia, 2) the bradycardia is vagally mediated, 3) MC4 receptors mediate these actions, and 4) the melanocortin input to the NA may be tonically active.Support: NIH grants HL024347 and HL076248.