TY - JOUR
T1 - Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation
AU - Zatta, Amanda
AU - Kin, Hajime
AU - Yoshishige, Darice
AU - Jiang, Rong
AU - Wang, Ningping
AU - Reeves, James
AU - Mykytenko, James
AU - Guyton, Robert
AU - Zhao, Zhi-Qing
AU - Caffrey, James
AU - Vinten-Johansen, Jakob
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://ajpheart.physiology.org/content/294/3/H1444.full.pdf
M3 - Article
VL - 294
SP - 1444
EP - 1451
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3
ER -