A proper analysis of the central nervous system mechanisms involved in the control of blood pressure relies heavily on a complete understanding of the neurochemical mechanisms involved in the processing of reflexes as well as the integration of centrally originating commands. The question of interaction between the different blood pressure control systems that operate in the normal state must be addressed and the morphological and neurochemical alterations that occur in the hypertensive state must be evaluated in light of alterations in: inputs, central integrating neurons and output neurons. Our hypothesis is that central adrenaline vasopressor systems are pathologically changed in the spontaneously hypertensive rat and that this system plays an important role in the development of spontaneous hypertension. We therefore propose to use the spontaneously hypertensive rat (SHR) and its normotensive control (WKY) rat to investigate neurochemical, neuroanatomical and developmental changes that occur in the brain stem and spinal cord. Our main emphasis is on monoaminergic systems in the medulla. Using a highly focused region of the central nervous system such as the nucleus of the tractus solitarius (nTS) as the basis for examining neurochemical differences between SHR and WKY rats, we hope to develop hypotheses and new data that will shed light on the role of other parts of the central nervous system involved in blood pressure regulaton. We propose to use a multifaceted approach to this problem, and will conduct in-depth studies on the nTS and blood pressure regulation. So far no information is available regarding the morphological and immunocytochemical changes that occur in essential hypertension. This project on the SHR rat will address that as a key question. The use of quantitation will enable us to make meaningful comparisons between hypertension (SHR) and normotension (WKY). The P.I. and co-P.I. have been collaborating for the past three years and complement each other in terms of technical and scientific skills. This project addresses the multifaceted question: What are the morphological and neurochemical errors in the central nervous system that are responsible for the development of essential hypertension?
