Sympathetic cardiovascular mechanisms are modified by chronic diseases, such as congestive heart failure, as well as by acute stress such as physical activity or exercise. The overall aim of this proposal is to understand the central mechanisms that contribute to the """"""""plasticity"""""""" of the arterial baroreceptor reflex arc. Hypothesis number 1: Contraction-induced activation of skeletal muscle receptors modulate the carotid baroreflex. Effect of mechanically and metabolically-sensitive hindlimb skeletal muscle afferent activity on carotid baroreceptor reflex function will be investigated. Carotid baroreceptors will be characterized using the isolated and perfused carotid sinus preparation in anesthetized dogs, and skeletal muscle receptors will be activated by ventral root stimulation and passive muscle stretch. Experiments will define the operational properties of the carotid baroreflex, as well as identify frequency-dependent characteristics of the reflex using transfer function analysis. Hypothesis number 2: Nucleus tractus solitarii (NTS) is the neural substrate for afferent baroreceptor and skeletal muscle receptor fibers. Skeletal muscle afferent fibers will be traced to the NTS using lectin-conjugated horseradish peroxidase (HRP) applied to the tibial nerve in cats. Colocalization of HRP- positive NTS neurons with Fos-positive neurons activated by muscle contraction will be determined utilizing immunohistochemical staining techniques. Hypothesis number 3: Afferent input from skeletal muscle receptors alters the excitability of barosensitive NTS neurons. Extracellular single- unit activity will be recorded from NTS neurons during controlled activation of the baroreflex and the skeletal muscle reflex using both canine and feline models. The primary focus of these studies is to determine the role for differential spike firing patterns in NTS neurons. The proposed experiments will be conducted at both the systems and the cellular levels. Results from these experiments will provide new information regarding the synaptic processing of visceral inputs by NTS neurons. This knowledge may help us to better understand the central mechanisms that alter arterial baroreflex control of cardiovascular function in both health and disease.
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