Release of catecholamines from the chromaffin cells of the adrenal medulla into the circulation plays a significant role in mediating the cardiovascular and autonomic changes that support the behavioral and physiologic responses to stresses that not only challenge the maintenance of homeostasis directly, such as hemorrhage, hypoxia, cold, pain, hypoglycemia or severe exercise, but also those in which the challenge is only perceived, such as fright, anger, danger, anxiety or emotional stress. The long term goals of this research are (1) to elucidate the elements and organization of the central neural pathways that specifically regulate adrenal medullary functions, (2) to increase our understanding of the behavioral properties and the neurotransmitter actions within this unique central autonomic circuit and (3) to use the network controlling adrenal epinephrine release as a model to determine the mechanisms that provide selective central control of functionally- specific sympathetic outputs and that regulate the sensitivity of different sympathetic effector systems to common reflex inputs. In the proposed research, electrophysiologic and pharmacologic approaches will be used in anesthetized rats (1) to test the hypothesis that sympathetic preganglionic neurons (SPNs) regulating the adrenal secretion of epinephrine constitute a unique population of splanchnic SPNs that can be distinguished from other SPNs by their characteristic responses to physiologic stimuli that alter adrenal medullary epinephrine release, (2) to determine how populations of brainstem neurons with demonstrated projections to adrenal SPNs, influence the discharge of the SPNs controlling epinephrine release and which spinal neurotransmitters are involved in mediating these responses, and (3) to determine the supraspinal components of reflex pathways mediating the responses of adrenal SPNs to (a) shifts in blood pressure (b) alterations in blood glucose, and ~ chemoreceptor activation. Finally, simultaneous brainstem and spinal cord unit recordings will be made to provide direct evidence for the hypothesis that adrenal medullary-specific, sympathoexcitatory neurons in the rostral ventrolateral medulla mediate the reflex responses and tonic excitatory drive to adrenal SPNs controlling epinephrine release. These studies will contribute new information on the organization and control of central sympathetic networks and will increase our understanding of the central mechanisms mediating a specific aspect of the cardiovascular responses to stress, injury and environmental challenge. The results could have implications for the control of such responses that are likely to arise during surgery or in disease conditions such as Raynaud~s diabetes, hypertension, cardiac failure and sepsis.
|Effective start/end date||1/1/97 → 12/31/01|
- National Institutes of Health: $238,071.00
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