Abstract

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL2 cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order to provide insights into the role of the beta adrenergic receptor system on lipoprotein cholesterol transport system. At 9 weeks of age (3 weeks of treatment), metoprolol significantly reduced LDL cholesterol concentration while propranolol had no detectable effect on this fraction. Both drugs significantly reduced HDL1 and HDL2 cholesterol concentration with the effect being somewhat greater with metoprolol than with propranolol. By 13 weeks of age (7 weeks of treatment), the differential effects of the beta blockers had disappeared.

Conventionally, the omnivorous rat is considered a low-ranking animal model for atherosclerosis-related studies because of its intrinsic refractoriness to atherosclerosis. In part II, we discovered the spontaneous severe hypercholesterolemic-atherosclerotic rat while investigating the contribution of prenatal dopamine-receptors down-regulation (haloperidol exposure) to age-related changes in rat aortic tissue. Besides providing an insight into a here-to-fore unrecognized dopamine-endocrine cholesterol homeostasis linkage, what emerges from these studies is that an autonomic nervous system receptor antagonist, haloperidol, when delivered during the early developmental period, permanently reverses an intrinsic refractoriness to atherosclerosis in rats.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Robert J. Boucek

Second Advisor

John Leonora

Third Advisor

Conrad M. van Gent

Fourth Advisor

Rodney Willard

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1989

Date (Title Page)

6-1989

Language

English

Library of Congress/MESH Subject Headings

Arteriosclerosis; Cholesterol; Adrenergic Beta Receptor Blockaders; Haloperidol

Type

Thesis

Page Count

v; 47

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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