Doctoral Dissertations

Date of Award

3-1987

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Life Sciences

Major Professor

James E. Lawer

Committee Members

Thomas Chen, Joel Lubar, Michael Sims

Abstract

The borderline hypertensive rat (BHR), the result of a cross between the normotensive Wistar-Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR), has been shown to be susceptible to hypertensinogenic blood pressure increases when exposed to particular shock-stress paradigms.

Brainstem and hypothalamic areas have been demonstrated to be involved in cardiovascular control in a regulatory or modulatory fashion. Several animal models of experimental hypertension, including the SHR, have been employed to demonstrate that aberrations of synthesis, release and turnover of central catecholamines may play a role in the development and maintenance of hypertension.

In this study, undertaken in an effort to determine if central catecholaminergic mechanisms might be involved in the stress-induced hypertension previously observed in the BHR, a total of eight groups of animals was used. Four control and four experimental groups were employed, with experimental animals, beginning at age fourteen weeks, being subjected to a predictable tail-shock for two hours daily for either three days or four, ten and sixteen weeks.

To determine if differences existed between animals exposed to stress and their control counterparts, a control and experimental group of BHR were sacrificed at each of the time points mentioned previously. Utilizing the Palkovits micropunch technique, three brainstem nuclei (A2, A1 and locus coeruleus) and seven hypothalamic nuclei (posterior, dorsomedial, lateral, ventromedial, paraventricular, anterior and supraoptic) were assayed for norepinephrine (NE), epinephrine (E), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA).

Comparisons between animals exposed acutely and chronically to the stress revealed, in acutely stressed BHR, a decrease in hypothalamic NE content, whereas in the chronically stressed animals, hypothalamic NE levels tended to increase. Further comparisons between experimental and control BHR revealed that the neurotransmitter most frequently observed to be different between groups was NE.

The DA data for control animals suggested a maturational role for this neurochemical in the BHR. Serotonin and its major metabolite, 5-HIAA, were observed to correlate most frequently with blood pressure levels in the experimental BHR.

Animals in this study did not develop the level of hypertension generally observed in the animal model when exposed to electroshock stress. This may be related to the predictability of the particular paradigm employed. It is possible that subpopulations of BHR may show an adaptability to the stress, perhaps with diminished sympathoadrenal-medullary activity, such that blood pressure elevations are minimized.

The differences in neurochemical content in the nuclei examined may reflect the response of the experimental BHR to the applied stress. Since the experimental groups did not develop significantly elevated blood pressures, it is possible that some of the changes in biogenic amine content detected may have been part of an apparently adaptive mechanism which prevented the inducement of the level of hypertension normally observed in the BHR exposed to such a stress.

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