Bradycardic effects of microinjections of urocortin‐III into the nucleus ambiguus in the rat

Abstract

Urocortin III, together with urocortin I and II, belongs to a family of stress peptides. Urocortin III mRNA has been reported to be expressed in the brainstem. The present investigation was carried out to test the hypothesis that microinjections of urocortin III into the nucleus ambiguus may elicit cardiac effects. Urethane-anesthetized, artificially ventilated, adult male Wistar rats, weighing between 300–350 gm, were used. Nucleus ambiguus (nAmb) was identified by microinjections of L-glutamate (L-Glu, 5 mmol/L, 30 nl). Microinjections (30–50 nl) of different concentrations (0.062, 0.125 and 0.25 mmol/L) of urocortin III into the nAmb elicited bradycardic responses (15 ± 2.9, 33 ± 3, and 47.5 ± 7.2 beats/min (bpm), respectively). These heart rate changes were not accompanied by any change in blood pressure. The bradycardic responses to maximally effective concentration of urocortin III (0.25 mmol/L) were significantly (p < 0.05) attenuated by prior microinjections of astressin (1 mmol/L; corticotropin releasing factor (CRF) receptor antagonist) into the nAmb. Bilateral vagotomy abolished the bradycardic responses to urocortin III. These results indicate that: Microinjections of urocortin III into the nAmb elicit bradycardia, the bradycardia was vagally mediated, and activation of CRF receptors was responsible for the actions of urocortin III. Support: NIH grants HL 24347 and HL076248.