The role of the central nervous system in the antihypertensive actions of propranolol and antenolol / by Eric D. Hawkins.
| Author/creator | Hawkins, Eric D. author. |
| Other author | Abdel-Rahman, Abdel A., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1992. |
| Description | 125 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Even though the mortality due to cardiovascular disease has decreased over the last several decades, hypertension is still the primary factor that closely relates to an increasing development of cardiovascular disease. Beta-adrenergic receptor antagonists (Beta-blockers) are a class of medications that competitively antagonize beta-adrenergic receptor agonists. Beta-blockers have been used clinically for several decades to treat cardiovascular disorders such as cardiac arrhythmia's, angina pectoris, and hypertension. A central nervous system site of action for the antihypertensive mechanism of beta-adrenergic antagonists has normally not been accepted because many believe that water-soluble drugs (e.g., atenolol) do not cross the blood-brain-barrier. Both propranolol and atenolol decrease blood pressure to similar degrees in hypertensive individuals. The major hypothesis tested by this investigation is that beta-blockers, lipid and water-soluble, gain access to the central nervous system of hypertensive animals and antagonize central beta-adrenergic receptors to at least partially explain their antihypertensive mechanism. In order to test this hypothesis, a lipid-soluble beta-blocker (e.g., propranolol) and a water-soluble beta-blocker (e.g., atenolol) were given chronically (5 weeks) to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Propranolol was used as a reference drug since its penetration into the central nervous system and antagonism of central beta-adrenergic receptors has been demonstrated. Following chronic treatment, hemodynamic responses were measured to centrally (ICV) injected isoproterenol. Dose-response curves were constructed and evaluated to pharmacologically quantitate the magnitude of blockade of central beta-adrenergic receptors. Evidence for penetration of beta-blockers into the central nervous system of SHR and WKY rats has been presented in this investigation A subhypothesis tested by this investigation was that spontaneously hypertensive rats, as compared to normotensive Wistar-Kyoto rats, have hyperexcitatory central beta-adrenergic receptors and demonstrate pressor responses to ICV injected isoproterenol. In order to test this hypothesis, hemodynamic dose-response curves to centrally (ICV) administered isoproterenol were compared between SHR and WKY rats. Evidence supporting a central nervous system hyperexcitatory beta receptor system regulating blood pressure control in hypertensive animals was not obtained in this investigation. |
| General note | Submitted to the faculty of the Department of Biology. |
| General note | Advisor: Abdel A. Abdel-Rahman |
| Dissertation note | M.S. East Carolina University 1992 |
| Bibliography note | Includes bibliographical references (leaves 118-125). |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | Access Content Online | ✔ Available |