Local opiate receptors in the sinoatrial node moderate vagal bradycardia

Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused int o the systemic circulation. This study was designed to locate the opiate re ceptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardi ac parasympathetic ganglia or the pre-junctional nerve terminals innervatin g the sinoatrial node. In this study 10 dogs were instrumented with a micro dialysis probe inserted into the sinoatrial node. The functional position o f the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimu lations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorde d on-line. MEAP was infused directly into the sinoatrial node via the micro dialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenor phine co-infused with MEAP MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultane ous local nodal blockade of these receptors with the opiate antagonist, dip renorphine, eliminated the effect of MEAP demonstrating the participation b y opiate receptors. Systemic infusions of MEAP produced a reduction in vaga l bradycardia nearly identical to that observed during nodal administration . When local nodal opiate receptors were blocked with diprenorphine, the sy stemic effect of MEAP was eliminated. These data lead us to suggest that th e opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-no dal or ganglionic receptors. (C) 2001 Elsevier Science B.V. All rights rese rved.