Repeated Arterial Occlusion, Delta-Opioid Receptor (DOR) Plasticity and Vagal Transmission Within the Sinoatrial Node of the Anesthetized Dog
| Autor: | Shekhar H. Deo, James L. Caffrey, Leticia Gonzalez, Matthew A. Barlow, Darice Yoshishige |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Microdialysis
medicine.medical_treatment Aorta Thoracic Blood Pressure Stimulation Vagotomy Synaptic Transmission General Biochemistry Genetics and Molecular Biology δ-opioid receptor Dogs Heart Rate Receptors Opioid delta Heart rate medicine Animals Ischemic Preconditioning Sinoatrial Node Sinoatrial node business.industry Vagus Nerve Naltrexone Blockade Vagus nerve medicine.anatomical_structure Anesthesia Ischemic preconditioning business |
| Zdroj: | Experimental Biology and Medicine. 234:84-94 |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.3181/0808-rm-242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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