Maximal inotropic response of electrically driven (0.5, 1 or 2 Hz) rat ventricular tissues in vitro to $ alpha sb1$-adrenoceptor agonist, methoxamine, was comparable to that of $ beta sb1$-adrenoceptor agonist isoprenaline up to 2 weeks of age. The inotropic effect of methoxamine decreased to adult levels at 3 weeks so that in tissues from rats 3 weeks and older, its inotropic effect was significantly less than that of isoprenaline. The inotropic effect of isoprenaline was not age-dependent. The inotropic effect of methoxamine was antagonized by prazosin and that of isoprenaline by propranolol. Treatment of pups at birth with dexamethasone, triiodothyronine or 6-hydroxydopamine did not influence that inotropic effect of methoxamine. Radioligand binding studies using $ sp3$(H) -prazosin and $ sp3$(H) -dihydroalprenolol as ligands and phentolamine and propranolol as displacers, respectively, revealed no age-dependent differences in myocardial $ alpha sb1$- and $ beta sp1$-adrenoceptor density or affinity. As well the increase in the second messenger inositol triphosphate (IP$ sb3$) after methoxamine was less in neonatal than in adult hearts. It is concluded that a greater inotropic effect of $ alpha sb1$-adrenoceptor agonists in neonatal rats may be due to unusual receptor-response coupling, which remains to be identified.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.69729 |
| Date | January 1993 |
| Creators | Inayatulla, Arjumand Bano |
| Contributors | Varma, D. R. (advisor) |
| 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 | Master of Science (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001351395, proquestno: AAIMM91843, Theses scanned by UMI/ProQuest. |
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