[Involvement of endogenous opioids in cardioprotective effects of ischemic preconditioning in the isolated rat heart].
In the present study, the relationship between the blockade of kappa-opioid receptor and ischemic preconditioning (IP) was examined and the effect of IP and prolonged ischemia on levels of dynorphin A1-13 (Dyn A1-13) in cardiac muscle in isolated perfused rat heart was investigated. The results are as follows: (1) IP reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), but had no significant effect on heart rate and coronary flow (P > 0.05); (2) MR2266, kappa opioid receptor antagonist, reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), and also enhanced the recovery of coronary flow, but had no significant effect on heart rate (P > 0.05); and (3) prolonged ischemia decreased the levels of Dyn A1-13 (P < 0.05), which was more marked in the unpreconditioned hearts. The results suggest: (1) MR2266 can "mimic" cardioprotective effect of IP in reducing the severity of arrhythmias and limiting infarct size of cardiac muscle; (2) ischemia causes release of endogenous kappa opioids, which can be attenuated by IP; and (3) the cardioprotective effects of IP in rat heart involves endogenous kappa opioids.
Fu
L L
LL
Department of Physiology, Zhejiang Medical University, Hangzhou 310031.
Xia
Q
Q
Shen
Y L
YL
Wong
T M
TM
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D001575:Benzomorphans / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004399:Dynorphins / Q000378:metabolism*; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*
D001575:Benzomorphans; D002316:Cardiotonic Agents; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; C027247:MR 2266; C026843:dynorphin (1-13); D004399:Dynorphins