Exogenous activation of delta- and kappa-opioid receptors affords cardioprotection in isolated murine heart.
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.
Peart
Jason N
JN
Dept. Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Gross
Garrett J
GJ
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism
D002316:Cardiotonic Agents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D007770:L-Lactate Dehydrogenase