NEUROTRANSMITTERS AND CENTRAL CONTROL OF BLOOD PRESSURE

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DESCRIPTION (Investigator's Abstract): Disturbances in the regulation of blood pressure may result from perturbations of transmitter mechanisms in the nucleus tractus solitarius (NTS), the site of termination of primary cardiovascular afferents. Thus, definition of the role played by putative transmitters in the NTS may increase understanding of central control of blood pressure. The principal investigator had previously shown that glycine (GLY) is released in the NTS. Micorinjection of the amino acid into the dorsal NTS elicits a depressor and bradycardiac response that is qualitatively like that of the excitatory amino acid glutamate (GLU), while injections into the ventral NTS and dorsal motor nucleus of the vagus (DMV) result in pressor, tachycardiac responses. Studies from the investigator's laboratory have supported a role for ACh, and have not supported glycine-glutamate receptor interactions in the mediation of these cardiovascular responses. The investigator will test the hypothesis that GLY elicits cardiovascular responses from the NTS through cholinergic mechanisms and specifically through the release of ACh. The role of GLY in the NTS in cardiovascular reflexes will be tested and projections from the functionally different sites in the NTS will be determined. The role of ACh in mediating the responses to GLY will be assessed and the mechanisms by which GLY leads to ACh release will be determined. Immunocytochemical methods will be used to identify and localize GLY-containing terminals and GLY receptors, and the relationship of those GLY elements to cholinergic neurons and nerve processes will be investigated. Finally, the relationship between GLY terminals and cardiovascular afferent fibers will be investigated to determine if GLY may be released from primary afferents or from interneurons within the NTS.