The long term objective of this proposal is to characterize the paracrine environment of the sinoatrial node of the dog. Specifically, we want to understand the actions of enkephalins and nitric oxide on heart rate control. We will use an innovative cardiac microdialysis technique to achieve this objective. We will also employ various agents such as NOS inhibitors and donors plus opioid agonists and antagonists to accomplish the following specific aims. This proposal will test the hypothesis that: MEAP acting on delta II opioid receptors located prejunctionally in the sinoatrial node suppresses vagal bradycardia by interrupting the NOcGMP pathway. 1. We will demonstrate that the delta II opioid receptor subtype is responsible for the vagolytic effect of nodal enkephalins. 2. That the NO-cGMP pathway in the SA node is required for normal vagal function in the dog. 3. That nodal MEAP suppresses vagal function by interrupting the NO-cGMP pathway. 4. That MEAP interrupts the NO-cGMP pathway prejunctionally in order to attenuate vagal bradycardia. Information obtained from this work will provide new insights into cardiac pathologies that involve autonomic dysfunction and may allow the creation of innovative therapies to help treat such pathologies.
| Farias 3rd, Martin; Jackson, Keith E; Yoshishige, Darice et al. (2003) Cardiac enkephalins interrupt vagal bradycardia via delta 2-opioid receptors in sinoatrial node. Am J Physiol Heart Circ Physiol 284:H1693-701 |
| Stanfill, Amber A; Jackson, Keith; Farias, Martin et al. (2003) Leucine-enkephalin interrupts sympathetically mediated tachycardia prejunctionally in the canine sinoatrial node. Exp Biol Med (Maywood) 228:898-906 |
| Farias, M; Jackson, K; Yoshishige, D et al. (2003) Bimodal delta-opioid receptors regulate vagal bradycardia in canine sinoatrial node. Am J Physiol Heart Circ Physiol 285:H1332-9 |
