Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Am J Physiol Heart Circ Physiol 294: H1444a??H1451, 2008. First published January 18, 2008; doi:10.1152/ajpheart.01279.2006.a??Opioids introduced at reperfusion (R) following ischemia (I) reduce infarct size much like postconditioning, suggesting the hypothesis that postconditioning increases cardiac opioids and activates local opioid receptors. Anesthetized male rats subjected to 30 min regional I and 3 h R were postconditioned with three cycles of 10 s R and 10 s reocclusion at onset of R. Naloxone (NL), its peripherally restricted analog naloxone methiodide, -opioid receptor (DOR) antagonist naltrindole (NTI), -opioid receptor antagonist norbinaltorphimine (NorBNI), and -opioid receptor (MOR) antagonist H-D-Phe-Cys- Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were administered intravenously 5 min before R. The area at risk (AAR) was comparable among groups, and postconditioning reduced infarct size from 57 2 to 42 2 (P 0.05). None of the antagonists alone altered infarct size. All antagonists abrogated postconditioning protection at higher doses. However, blockade of infarct sparing by postconditioning was lost, since tested doses of NL, NTI, NorBNI, and CTAP were lowered. The efficacy of NorBNI declined first at 3.4 mol/kg, followed sequentially by NTI (1.1), NL (0.37), and CTAP (0.09), suggesting likely MOR and perhaps DOR participation. Representative small, intermediate, and large enkephalins in the AAR were quantified (fmol/mg protein; mean SE). I/R reduced proenkephalin (58 9 vs. 33 4; P 0.05) and sum total of measured enkephalins, including proenkephalin, peptide B, methionine-enkephalin, and methionine- enkephalin-arginine-phenylalanine (139 17 vs. 104 7; P 0.05) compared with shams. Postconditioning increased total enkephalins (89 8 vs. 135 5; P 0.05) largely by increasing proenkephalin (33 4 vs. 96 7; P 0.05). Thus the infarct-sparing effect of postconditioning appeared to involve endogenously activated MORs and possibly DORs, and preservation of enkephalin precursor synthesis in the AAR.
|Pages (from-to)||1444 - 1451|
|Number of pages||8|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Publication status||Published - 2008|