Delayed uncoupling is related to cardioprotection induced by kappa-agonist U-50,488H in rat heart.
OBJECTIVE
To determine whether the kappa-opioid receptor agonist U50,488H affects electrical uncoupling during prolonged ischemia and, if so, whether the changes are associated with its cardioprotective action.


METHODS
The isolated rat heart was perfused in a Langendorff apparatus. Formazan content, lactate dehydrogenase (LDH) and hemodynamic parameters were measured to confirm the cardioprotective effect of U50,488H. The effects of U50,488H on electrical coupling during prolonged ischemia were also measured.


RESULTS
U50,488H concentration-dependently increased formazan content and reduced LDH release, and the ameliorating effect of 10(-5) mol/L U50,488H was abolished by 5 x 10(-6) mol/L nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist, or 10(-4) mol/L 5-hydroxydecanoate (5-HD), a selective mitochondrial ATP-sensitive K(+) (K(ATP)) channel blocker. The onset of electrical uncoupling during prolonged ischemia was delayed by U50,488H, and the delay was not only abolished, but also advanced by nor-BNI or 5-HD relative to the control group.


CONCLUSIONS
These results demonstrate that delayed uncoupling during prolonged ischemia is associated with the cardioprotection of U50,488H, and these effects of U50,488H are mediated by mitochondrial K(ATP) channels.
Chen
Bao-Ping
BP
Department of Physiology, Shaoxing University School of Medicine, Shaoxing, 312000, China.
Mao
Hong-Jiao
HJ
Fan
Fang-Yan
FY
Bruce
Iain C
IC
Xia
Qiang
Q
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002450:Cell Communication; D022062:Electrophysiologic Techniques, Cardiac; D005562:Formazans; D017629:Gap Junctions / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013997:Time Factors
D002316:Cardiotonic Agents; D005562:Formazans; D050883:HSC70 Heat-Shock Proteins; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; C117780:mitochondrial K(ATP) channel; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer