PATHWAYS INTEGRATING STRESS AND CARDIOVASCULAR RESPONSES

拟议的研究旨在澄清组织和

The proposed studies are designed to clarify the organization and neuropeptide content of afferent projections to the paraventricular nucleus of the hypothalamus (PVH) that provide for the integration of stress and cardiovascular responses, and to determine whether exposure to various stress models can effect alterations in the expression of corticotropin-releasing factor (CRF) and other peptidergic stimulators of adrenocorticotropic hormone secretion by parvocellular neurosecretory neurons in the PVH. Sensitive new retrograde transport (of fluorescent tracers) and anterograde transport (of the lectin, PHA-L0 methods will be combined with single- and multiple-immunohistochemical staining techniques to address four basic issues. (i) Two potential routes for the mediation of cognitive influences on stress peptide secretion from the PVH will be examined. One involves local inputs from cells in the perinuclear zone immediately surrounding the PVH; the second involves an established pathway from the bed nucleus of the stria terminalis that requires further characterization. (ii) The organization of neuropeptide Y (NPY)-containing inputs to the PVH will be delineated, with special attention given to clarifying the extent to which NPY-immunoreactivity is co-localized within catecholaminergic pathways whose roles in effecting stress and cariovascular responses are more clearly established. (iii) The distribution, cells of origin, and biochemical makeup of a new and potentially major projection to the PVH from the lateral dorsal tegmental nucleus will be determined. (iv) The level of expression in the PVH of CRF and other peptidergic secretagogues for corticotropin (vasopressin, angiotensin II) will be compared in stressed and normal animals. Collectively, these studies will identify neuropeptides contained within pathways for the initiation of stress and cariovascular responses, and will indicate the nature and extent of their involvement. In addtiion, they will begin to elucidate how peptide expression within the system may be modified underconditions of stress. The work is therefore most relevant to health problems associated with chronic stress and hypertension.