The Brain Renin-Angiotensin System: Biochemical Characterization and Possible Role in Hypertension
Meyer, Joan Marie
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Permalink
https://hdl.handle.net/2142/77681
Description
Title
The Brain Renin-Angiotensin System: Biochemical Characterization and Possible Role in Hypertension
Author(s)
Meyer, Joan Marie
Issue Date
1986
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Neuroscience
Language
eng
Abstract
A renin-angiotensin system (RAS) endogenous to the brain has been proposed on the basis of immunochemical, biochemical and pharmacological evidence. Angiotensin II exerts potent effects in CNS tissues and appears to be involved fluid balance homestasis and blood pressure regulation. The data in this thesis provides additional evidence for a functional RAS in the brain and provides possible insight into the role of this system in the pathophysiology of hypertension.
The ability of neurons to synthesize ANG II was investigated using primary cultures of dissociated fetal rat brain cells. Cells were incubated with a ('3)H-amino acid precursor and the time-dependent incorporation of the precursor into de novo synthesized ANG II was investigated using radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). The biological activity of the newly synthesized ANG II was investigated by the intraventricular administration of the product to Sprague-Dawley rats and observing subsequent changes in blood pressure.
To lend further support to the role of ANG II as a neuromodulator/neurotransmitter, the release of ANG II from presynaptic nerve terminals was investigated using the primary cell culture system. Cells were challenged with a concentration of potassium chloride (KCl) sufficient to cause depolarization and the release of ANG II into the culture medium measured by RIA and HPLC. Release of ANG II was found to be a calcium-dependent phenomenon, as absence of calcium from the incubating medium resulted in no detectable levels of ANG II even in the presence of the KCl.
A possible role for brain ANG II as a neuromodulator/neurotransmitter was studied by measuring levels of the peptide by RIA in microdissected brain nuclei in the developing spontaneously hypertensive rat (SHR) and normotensive control Wistar Kyoto rat (WKY). By the time measurable differences in blood pressure are evident between the two strains, there are differences in ANG II levels in some nuclei implicated in cardiovascular control. Levels of ANG II change within strains during development. These data provide additional support for the involvement of ANG II in the pathogenesis of hypertension in the SHR.
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