The role of $ beta$-endorphin in the cardiovascular depressor response elicited by clonidine or by electrical stimulation of the nucleus tractus solitarii (NTS) was studied in awake as well as anesthetized rats. The opiate antagonists, naloxone or naltrexone, inhibited the hypotensive and bradycardic effects of clinidine in spontaneously hypertensive rats (SHR), in normotensive and steroid-salt hypertensive Sprague-Dawley (S-D) rats, but not in normotensive Wistar Kyoto (WKY) rats. The brain ACTH/$ beta$-endorphin fibre system originating in the arcuate nucleus was eliminated by neonatal treatment with monosodium glutamate (MSG). MSG-treatment abolished the naloxone-sensitive component of the effects of clonidine in SHR, while the naloxone-resistant effects of clonidine in WKY were not affected. Intra-NTS microinjection of clonidine (5 nmol) decreased blood pressure and heart rate, and these effects were inhibited by previous intra-NTS injection of dl- but not d-naloxone (270 pmol) in both SHR and normotensive S-D rats. Intra-NTS injection of $ beta$-endorphin (0.3 pmol) also reduced blood pressure and heart rate in both rat strains. In SHR, the effects of both clonidine and $ beta$-endorphin were inhibited by ICI 174864, a selective $ delta$ receptor antagonist, but not by $ beta$-funaltrexamine, a selective $ mu$ receptor antagonist (270 pmol, intra-NTS). In contrast, in normotensive S-D rats only the $ mu$ and not the $ delta$ antagonist was an effective inhibitor. In S-D rats made hypertensive by prolonged treatment with a mineralocorticoid and salt, the pattern of inhibition was the same as in SHR. The depressor baroreflex response was elicited by electrical stimulation of the NTS. In SHR, intra-NTS injection of an antiserum to $ beta$-endorphin inhibited, while an antiserum to met-enkephalin potentiated the hypotensive and bradycardic response to NTS stimulation. In similar experiments in WKY rats, the antisera were ineffective. / These findings are interpreted to indicate that the cardiovascular effects of clonidine involve release of $ beta$-endorphin and subsequent stimulation of opiate receptors in the NTS. The most likely source of $ beta$-endorphin is nerve terminals whose cell bodies are in the arcuate nucleus. The released $ beta$-endorphin acts on $ mu$ receptors in normotensive or $ delta$ receptors in hypertensive rats, with no evidence for the additional involvement of peripheral opiate receptors. (Abstract shortened with permission of author.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.75445 |
| Date | January 1987 |
| Creators | Mosqueda-Garcia, Agustin Rogelio |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000547708, proquestno: AAINL44387, Theses scanned by UMI/ProQuest. |
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