The possible role of endogenous opioids in the central adrenergic control of blood pressure and heart rate was studied in different strains of hypertensive and normotensive rats. In spontaneously hypertensive rats (SHR) the hypotension and bradycardia resulting from stimulation of central (alpha)-adrenoceptors by clonidine or (alpha)-methyldopa are inhibited by the opiate antagonists naloxone and naltrexone and by centrally administered (beta)-endorphin antibody. Clonidine and 1-(alpha)-methylnoradrenaline increase the release of immunoreactive (beta)-endorphin from brain stem slices of SHR, superfused in vitro. The antihypertensive effects of clonidine and (alpha)-methyldopa are similarly inhibited by opiate antagonists in steroid/salt and renal hypertensive, Sprague-Dawley rats, but not in matched normotensive controls for the above three groups of animals. Furthermore, in SHR the centrally mediated acute as well as the chronic antihypertensive action of propranolol is prevented or reversed by naloxone and naltrexone, whereas the hypotensive response to baroreflex activation or to direct electrical stimulation of the nucleus of the solitary tract (NTS) is not inhibited and the bradycardia is potentiated by naltrexone. These findings indicate that the mechanism of action of antihypertensive drugs that act through stimulation (alpha)(,2)-adrenoceptors in the central nervous system involves the release of an endorphin-like opioid from the brainstem and subsequent stimulation of opiate receptors inhibitory to sympathetic tone. The exact central site of this interaction is not known, but in SHR it does not appear to involve the NTS or another component of the baroreflex arc. Finally, the adrenergic-opioid interaction is absent or inactive in normotensive animals, and it appears to be activated by the hypertensive process.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.71852 |
| Date | January 1982 |
| Creators | Ramirez-Gonzalez, Maria Dolores. |
| 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: 000176403, proquestno: AAINK64624, Theses scanned by UMI/ProQuest. |
Page generated in 0.0024 seconds