This study will identify specific brain sites, receptor types, neuronal networks peripheral effecter mechanism and neuro-transmitters involved in cardiovascular regulation in an attempt to better understand the underlying mechanisms influencing hyper-tension. Preliminary studies in our laboratory have shown that hypothalamic microinjections of neurotensin (NT) aimed for the paraventricular nucleus (PVH) causes a substantial increase in mean atrial blood pressure (MABP) in the anesthetized rat. The specific mechanisms involved in these responses, however are unknown. The presence of nerve terminals within the PVR which originate from cardiovascular (CV) regulatory areas of the brain site which Influences CV regulation. We also suspect NT, due to its endogenous presence within the PVH, of being a major neurotransmitter acting within this nucleus. Therefore, our studies will further investigate NT mediated participation of the PVH in CV responses. Male Sprague-Dawley rats will receive stereotaxic microinjections of NT into the PVH. Indwelling catheters and a polygraph will be used to monitor MABP, right atrial pressure and heart rate. The experimental design will utilize four experimental groups to determine: (a) if the PVH is the brain site most sensitive to NT; by injecting it into regions immediately surrounding the PVH and those nuclei with high concentrations of NT, (b) the involvement of local alpha-adrenoceptors in NT responses; by blocking alpha1 and alpha2 adrenoceptors by pretreating the animal with corynathine hydrochloride and rauwolscine hydrochloride respectively and by destruction of catecholaminergic nerve terminals with the neurotoxin 6-hydroxydopamine followed by NT injection, and (d) the involvement of the following effecter systems by eliminating prior to NT injection these activities: 1) the sympathetic nervous system by treatment with guanethidine, 2) the adrenal gland by bilateral adrenalectomy and 3) vagal nerve activities, arginine vasopressin and angiotensin II by pretreatment with their specific antagonist, atropine methyl nitrate, TME-AVP and captropril, respectively, prior to NT injection.
