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?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033632-05
Application #
3345716
Study Section
(SRC)
Project Start
1984-09-30
Project End
1990-09-29
Budget Start
1988-09-30
Budget End
1990-09-29
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Kalia, M (1991) Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons. Brain Res 548:111-25
Kalia, M; Richter, D (1988) Rapidly adapting pulmonary receptor afferents: I. Arborization in the nucleus of the tractus solitarius. J Comp Neurol 274:560-73
Kalia, M P (1987) Organization of central control of airways. Annu Rev Physiol 49:595-609
Bose, B; Osterholm, J L; Kalia, M (1986) Ganglioside-induced regeneration and reestablishment of axonal continuity in spinal cord-transected rats. Neurosci Lett 63:165-9
Kalia, M; Richter, D (1985) Morphology of physiologically identified slowly adapting lung stretch receptor afferents stained with intra-axonal horseradish peroxidase in the nucleus of the tractus solitarius of the cat. II. An ultrastructural analysis. J Comp Neurol 241:521-35
Kalia, M; Richter, D (1985) Morphology of physiologically identified slowly adapting lung stretch receptor afferents stained with intra-axonal horseradish peroxidase in the nucleus of the tractus solitarius of the cat. I. A light microscopic analysis. J Comp Neurol 241:503-20
Kalia, M; Fuxe, K (1985) Rat medulla oblongata. I. Cytoarchitectonic considerations. J Comp Neurol 233:285-307
Kalia, M; Woodward, D J; Smith, W K et al. (1985) Rat medulla oblongata. IV. Topographical distribution of catecholaminergic neurons with quantitative three-dimensional computer reconstruction. J Comp Neurol 233:350-64
Kalia, M; Fuxe, K; Goldstein, M (1985) Rat medulla oblongata. III. Adrenergic (C1 and C2) neurons, nerve fibers and presumptive terminal processes. J Comp Neurol 233:333-49