The identification and specific role of the neurotransmitters involved in the central neural control of the circulation in perturbations such as exercise are topics of much experimentation and controversy at the present time. Resolution of these issues is important because our understanding of the central neural events behind autonomic control is incomplete without this information. Furthermore, the application of these data may lead to revisions in the pharmacological strategies for treatment of cardiovascular diseases. Some of the most critical areas of the central nervous system which participate in blood pressure (BP) and heart rate (HR) regulation are: 1) the intermediolateral cell column (IML) containing the cell bodies of the preganglionic sympathetic neurons and 2) various medullary areas, including the ventrolateral medulla (VLM), the raphe nuclei (RN) and the parapyramidal region of the,ventromedial medulla (VMM) which in turn are major medullary outflow pathways to the IML. The nature of chemical transmission within these areas are the focus of this proposal. It is a matter of common everyday experience that BP and HR are raised during exercise. This research will study models of neural mechanisms thought underlie these changes during exercise. One model is centrally mediated, relying on stimulation of the higher centers such as the hypothalamus to raise BP and HR. The other, the primary focus of this proposal, is a model of reflex mechanisms in exercise responses- stimulation of the ventral roots to induce muscular contraction (VRSMC), which in turn raises BP and HR. It is also important to study the transmitters mediating the reciprocal action (depressor) of the baroreceptor reflex (baroreflex) as it is thought to be inactivated during pressor events. Thus, we also wish to monitor the chemical events during the baroreflex-to determine the transmitters released due to an isolated baroreflex input so as to be aware of the significance of any changes in these transmitters during the pressor events associated with exercise. We will identify, using microdialysis and single cell recording combined with microiontophoresis: First, which substances are increased or attenuated at the level of the IML during: 1) VRSMC, 2) baroreflex stimulation and 3) stimulation of selected brainstem sites. Second, what chemicals are increased or attenuated at selected brainstem i pressor sites during: 1) VRSMC 2) baroreflex stimulation and 3) stimulation of selected diencephalic and other brainstem sites thought to modulate pressor information.
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