Exogenous activation of delta- and kappa-opioid receptors affords cardioprotection in isolated murine heart. Basic Res Cardiol 2004 Jan;99(1):29-37
Date
12/20/2003Pubmed ID
14685703DOI
10.1007/s00395-003-0430-yScopus ID
2-s2.0-0346368469 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
Controversy exists regarding the relative roles of delta- and kappa-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 delta - and kappa-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 micro M), lead to a marked improvement in post-ischemic contractile recovery where LVDP returned to 65.5 +/- 2.4% of baseline function. The delta-opioid selective agonist BW373U86 hydrochloride elicited maximal protection at a concentration of 1 micro M which afforded 63.9 +/- 3.4% recovery of LVDP. This effect was blocked by the delta-opioid selective antagonist, BNTX. Furthermore, administration of the kappa-opioid selective agonist U50,488 (1 micro M) 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 kappa-opioid receptor antagonist, nor-BNI. No differences were noted in LDH efflux from post-ischemic hearts. These data suggest that exogenous activation of delta- and kappa-opioid receptors afford protection against myocardial stunning in the isolated murine heart, an effect attenuated by selective receptor antagonists.
Author List
Peart JN, Gross GJMESH terms used to index this publication - Major topics in bold
AnimalsCardiotonic Agents
Enzyme Activation
Heart
In Vitro Techniques
Ischemic Preconditioning, Myocardial
L-Lactate Dehydrogenase
Male
Mice
Mice, Inbred C57BL
Myocardial Ischemia
Myocardial Reperfusion Injury
Receptors, Opioid, delta
Receptors, Opioid, kappa
