Fentanyl activates a particular population of vagal efferents which are cardioinhibitory.

In order to determine whether and how opiates affect vagal efferents, effects of fentanyl on single fibre discharge in the cervical vagus in dogs were studied. Dependent upon the responses to induced increases in blood pressure, 3 types of vagal efferents were classified: Type A (n = 9) with an increase, type B (n = 4) with a decrease and type C (n = 27) with no change in rate of discharge. Fentanyl (0.01 mg/kg i.v.) activated type A efferents which are considered as cardioinhibitory, but it did not activate type B and type C efferents. The activation was antagonized by naloxone. Cumulative doses of fentanyl (0.0025-0.16 mg/kg i.v.) produced a progressive increase in the discharge rate of type A efferents and a decrease in heart rate. These effects were maximum at 0.04 mg/kg (n = 7). Blood pressure was only slightly affected. The changes in discharge rate and heart rate were strongly and negatively correlated (r = -0.82, P less than 0.001). At maximum cardioinhibitory effects of fentanyl, blood pressure increases were able to further activate type A efferents and to decrease heart rate. The results show that fentanyl acts differentially on various vagal efferents. Only type A (cardioinhibitory) efferents are activated. It is hypothesized that the opiate receptor system in the brain plays a physiological role in the control of heart rate.