[D-Met2,Pro5]enkephalinamide activates cardioinhibitory efferents in anaesthetized dogs

[D-Met2,Pro5]enkephalinamide (DMPEA) strongly activated cardioinhibitory vagal efferents and elicited bradycardia when perfused through the cerebroventricular system of anaesthetized dogs. These effects were concentration-dependent but plateaued at an intraventricular concentration of 200 micrograms/ml. At this maximally effective concentration, the vagal discharge rate was fourfold higher and the heart rate was lowered by 28% compared to the controls. These effects were reversed by naloxone (40 micrograms/ml). There was no significant change in blood pressure. Vagal discharge rate and heart rate correlated closely and inversely with each other with r values ranging between -0.75 and -0.95. Opiate receptors in brain structures bordering the cerebroventricular system are the most likely mediators of the effects of DMPEA. The opiate receptor/endorphin system may therefore play a role in the physiological control of cardiac vagal tone and thus of heart rate.