The aims of this project are to obtain detailed morphological information about the neuroanatomical substrate for the development of hypertension following interruption of the baroreflex pathway in the vicinity of the nTS in the dog, and to evaluate the importance of catecholamines and selected neuropeptides in this form of neurogenic hypertension. The proposed studies are intended first to evaluate the extent and variety of neuropathological changes in the brain stem which follow destruction of the baroreceptor reflex pathway in the vicinity of the nTS. Because the morphology of the canine nTS has not been detailed, we must first examine its structure. Then neuropathological analysis will be employed to assess the changes in the nTS following hypertension producing lesions. Silver degeneration will allow tracing of damaged pathways into other areas of the brain stem. Horseradish peroxidase will be used to investigate survival of vagal and carotid sinus afferents and efferents following lesions. These investigations will be undertaken during Phase 1 of the Physician Scientist Award concurrently with intensive training in neuroanatomical techniques. The demonstration by this laboratory of the interaction in the dog's brain stem between peptidergic and neurogenic mechanisms emphasizes importance of studies localizing these neurochemicals and the extent and means of their participation in cardiovascular control and central neurogenic hypertension. There is evidence for both the participation of endogenous opiates in the pressor response to angiotensin II mediated by the area postrema and the role of vasopressin in modulating these central effects of Ang II. In addition, the interactions between Ang II and norepinephrine in the CNS are well known. Thus we will map the catecholamines and the neuropeptides angiotensin II, vasopressin and enkephalin in ghe dog's brain stem. The proposed Phase II studies will form part of the ongoing effort in this laboratory to detail the distribution of these substances, and will focus upon the relationships of the alterations in these neurochemicals following lesions to the neuropathological changes which characterize the production of hypertension by destruction of the baroreceptor relay in the vicinity of the nTS.
| Estes, M L; Block, C H; Barnes, K L (1989) The canine nucleus tractus solitarii: light microscopic analysis of subnuclear divisions. Brain Res Bull 23:509-17 |
