Date of Award

1-1-1987

Embargo Period

11-20-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology

College

College of Graduate Studies

First Advisor

Phillip J. Privitera

Second Advisor

Thomas Walle

Third Advisor

Rosalie K. Crouch

Abstract

The contribution of the central nervous system to the hypotensive action of atenolol was examined in spontaneously hypertensive rats and normotensive dogs. In the rat, atenolol produced a hypotensive response which was stereoselective for the ��-isomer after both central and peripheral administration. In addition, 10 µg ��-atenolol administered intra-cisternally produced a hypotensive response not observed after intravenous administration of the same dose. The hypotensive action of atenolol was further examined using a method developed for the quantita­tion of atenolol in plasma and cerebrospinal fluid (CSF) of dogs. Atenolol rapidly entered the CSF after intravenous administration, producing a hypotensive response in association with an increase in CSF norepinephrine levels. Furthermore, after chronic oral treatment, atenolol was accumulated in brain tissue and released into the CSF along with norepinephrine in response to central administration of the norepinephrine-releasing drug tyramine. These data suggest that atenolol may act presynaptically to release norepinephrine from central noradre­nergic neurons, which may in turn result in a hypotensive response.

Rights

All rights reserved. All rights reserved. Copyright is held by the author.

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