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The Cardiovascular Actions of Mu and Kappa Opioid Agonists in vivo and in vitro.

Omoniyi, Abimbola T. (1998) The Cardiovascular Actions of Mu and Kappa Opioid Agonists in vivo and in vitro. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

The effects of two selective μ-opioid agonists DAMGO and DALDA, and a selective κ-opioid agonist U50,488H on blood pressure and heart rate have been compared in the chronically instrumented and awake sheep. Differences in the heart rate response to μ- and κ-opioid agonists in vivo were demonstrated. The mechanism behind the heart rate response to all three opioid agonists was investigated by studying the effects of μ- and κ-agonists on baroreflex sensitivity and the involvement of sympathetic activity in the heart rate response to κ-opioid agonists. The site and mechanism of action involved in the effects of DAMGO and DALDA on the baroreflex were further investigated in vivo. The opioid receptor agonists involved in these studies are undergoing development as obstetrical analgesics for clinical use hence the influence of pregnancy on the effects of μ- and κ-opioid agonists on blood pressure, heart rate and baroreflex sensitivity were investigated. The mechanism responsible for the blood pressure effects of μ-opioid agonists observed in vivo was investigated in vitro using the isolated and perfused guinea pig heart. The effects of DAMGO and DALDA on inotropy, chronotropy and coronary flow has been demonstrated in the spontaneously beating heart. Differences in the inotropic response to DAMGO and DALDA in the absence of their chronotropic influence was demonstrated in electrically paced hearts. Inotropic responses to DAMGO and DALDA have been shown to be influenced by the contractile condition of the heart. The potential therapeutic efficacy of μ-opioid agonists has been investigated by studying the development of tolerance to their cardiovascular effects in vivo and in vitro. DAMGO and DALDA have been shown to induce rapid tolerance to blood pressure responses and inotropic responses in vivo and in vitro respectively. Differences in the relative potencies of DAMGO and DALDA was confirmed in all studies.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Omoniyi, Abimbola T.
Date : 1998
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1998.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:23
Last Modified : 06 May 2020 14:29
URI: http://epubs.surrey.ac.uk/id/eprint/856164

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