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- Title
Exogenous activation of δ- and κ-opioid receptors affords cardioprotection in isolated murine heart.
- Authors
Peart, Jason N.; Gross, Garrett J.
- Abstract
Controversy exists regarding the relative roles of δ- and κ-opioid receptor activation as a potential cardioprotective mechanism. Furthermore, the function of opioid receptor activation in cardioprotection has not been examined in the murine heart. To this end, we employed various concentrations of selective δ - and κ-opioid receptor agonists in an isolated murine heart model undergoing 20 min global ischemia followed by 45 min reperfusion. Left-ventricular developed pressure (LVDP) returned to 50.7 ± 2.1% of baseline values in untreated hearts. Infusion of the non-selective opioid agonist, morphine (10 µM), lead to a marked improvement in post-ischemic contractile recovery where LVDP returned to 65.5 ± 2.4% of baseline function. The δ-opioid selective agonist BW373U86 hydrochloride elicited maximal protection at a concentration of 1 µM which afforded 63.9 ± 3.4% recovery of LVDP. This effect was blocked by the δ-opioid selective antagonist, BNTX. Furthermore, administration of the κ-opioid selective agonist U50,488 (1 µM) produced a marked improvement in contractile recovery leading to a 72.5 ± 5.3% recovery of LVDP. This degree of protection was also abolished by the κ-opioid receptor antagonist, nor-BNI. No differences were noted in LDH efflux from post-ischemic hearts. These data suggest that exogenous activation of δ- and κ-opioid receptors afford protection against myocardial stunning in the isolated murine heart, an effect attenuated by selective receptor antagonists.
- Subjects
OPIOID receptors; HEART; ISCHEMIA; CORONARY disease; OPIOIDS; MORPHINE
- Publication
Basic Research in Cardiology, 2004, Vol 99, Issue 1, p29
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-003-0430-y