Repeated arterial occlusion, delta-opioid receptor (DOR) plasticity and vagal transmission within the sinoatrial node of the anesthetized dog

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 234; no. 1; p. 84
• Main Authors: Deo, Shekhar H, Barlow, Matthew A, Gonzalez, Leticia, Yoshishige, Darice, Caffrey, James L
• Format: Journal Article
• Language: English
• Published: England 01.01.2009
• Subjects: Animals; Aorta, Thoracic - physiology; Blood Pressure; Dogs; Heart Rate; Ischemic Preconditioning; Microdialysis; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Receptors, Opioid, delta - physiology; Sinoatrial Node - physiology; Synaptic Transmission - physiology; Vagotomy; Vagus Nerve - physiology
• ISSN: 1535-3702
• DOI: 10.3181/0808-RM-242

Brief interruptions in coronary blood flow precondition the heart, engage delta-opioid receptor (DOR) mechanisms and reduce the damage that typically accompanies subsequent longer coronary occlusions. Repeated short occlusions of the sinoatrial (SA) node artery progressively raised nodal methionine-enkephalin-arginine-phenylalanine (MEAP) and improved vagal transmission during subsequent long occlusions in anesthetized dogs. The DOR type-1 (DOR-1) antagonist, BNTX reversed the vagotonic effect. Higher doses of enkephalin interrupted vagal transmission through a DOR-2 mechanism. The current study tested whether the preconditioning (PC) protocol, the later occlusion or a combination of both was required for the vagotonic effect. The study also tested whether evolving vagotonic effects included withdrawal of competing DOR-2 vagolytic influences. Vagal transmission progressively improved during successive SA nodal artery occlusions. The vagotonic effect was absent in sham animals and after DOR-1 blockade. After completing the PC protocol, exogenously applied vagolytic doses of MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of these DOR-2 vagolytic effects was small compared to controls and repeated MEAP challenges rapidly eroded vagolytic responses further. Prior DOR-1 blockade did not alter the PC mediated, progressive loss of DOR-2 vagolytic responses. In conclusion, DOR-1 vagotonic responses evolved from signals earlier in the PC protocol and erosion of competing DOR-2 vagolytic responses may have contributed to an unmasking of vagotonic responses. The data support the hypothesis that PC and DOR-2 stimulation promote DOR trafficking, and down regulation of the vagolytic DOR-2 phenotype in favor of the vagotonic DOR-1 phenotype. DOR-1 blockade may accelerate the process by sequestering newly emerging receptors.