title: Repeated arterial occlusion, delta-opioid receptor (DOR) plasticity and vagal transmission within the sinoatrial node of the anesthetized dog.
abstract: 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.
authors.affiliation: University of North Texas Health Science Center, Department of Integrative Physiology, Cardiovascular Research Institute, Fort Worth, TX 76107, USA.
authors.forename: Shekhar H
authors.initials: SH
authors.lastname: Deo
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Barlow
authors.forename: Leticia
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Darice
authors.initials: D
authors.lastname: Yoshishige
authors.forename: James L
authors.initials: JL
authors.lastname: Caffrey
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001794:Blood Pressure; D004285:Dogs; D006339:Heart Rate; D019194:Ischemic Preconditioning; D017551:Microdialysis; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000502:physiology*; D012849:Sinoatrial Node / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D017465:Receptors, Opioid, delta; D009271:Naltrexone