NEUROPHARMACOLOGY OF THE BARORECEPTOR REFLEX

本研究的主要目的是识别和

The principal aim of this research is the identification and characterization of neural pathways, neurotransmitters and synaptic receptors which participate in central autonomic and cardiovascular regulation. Three important integrative "centers" in the medulla oblongata have been identified which play a major role in central cardiovascular control. These are: 1) the nucleus of the tractus solitarius (NTS), 2) the caudal ventrolateral medulla (CVM), and 3) the rostral ventrolateral medulla (RVM). These medullary regions appear to be linked within a neural network that regulates the activity of the peripheral sympathetic nervous system. However, the precise functional and anatomical relationship between these areas, as well as the neurotransmitters and synaptic receptors responsible for information transmission between them, and other brain regions have not been well characterized. The proposed research will provide convergent lines of physiological, pharmacological, biochemical and anatomical evidence with which to address this question. The first Specific Aim will be to evaluate the role of the CVM and RVM in central baroreflex, cardiovascular and respiratory regulation. These experiments will employ electrolytic lesions and microinjection of drugs int the medulla to: 1) confirm the role of the CVM in central baroreflex control, 2) determine if the CVM plays a role in central sympthoinhibitory processes independently of baroreceptor reflexes, 3) identify the excitatory amino acid (EAA) receptor types in the RVN which are responsible for mediating neural transmission of sympathoexcitatory information, and 4) determine whether the CNS pathways and synaptic receptors which mediate cardiovascular reflexes can be distinguished from those which underlie respiratory reflexes evoked by identical stimuli. The second Specific Aim is to examine at the biochemical level the function of amino acid neurotransmitters in central cardiovascular control. Activation of central baroreflex and sympathoexcitatory pathways combined with in vivo microdialysis of the RVM and CVM will be used to measure local EAA and GABA release coincident with stimulation. In addition, selective destruction of afferent cardiovascular pathways projecting to these medullary sites combined with in vitro neurochemical analyses of tissue micropunches of the CVM and RVM will be employed to further assess the role of EAA's and GABA in medullary baroreflex and cardiovascular regulation. The third Specific Aim will examine the anatomical relationship between functionally identified "cardiovascular" regions in the medulla. These experiments are designed to provide the structural foundation to complement the functional results obtained from the studies outlined under Specific Aims 1 and 2. Knowledge of the organization and neuropharmacology of central cardiovascular control may help to provide a rational basis for the design of drugs useful for treating pathological abnormalities such as hypertension.