Opioid δ(1) and δ(2) receptor agonist attenuate myocardial injury via mPTP in rats with acute hemorrhagic shock.
BACKGROUND
Studies have documented the beneficial roles of δ opioid receptor (OR) agonist for hemorrhagic shock. However, the myocardial protection roles and the mechanisms of hemodynamic stability during resuscitation of δ-OR agonist have not been explored. This study was designed to investigate myocardial protective effects and the mechanisms of high selective δ(1) and δ(2)-OR agonists during resuscitation of acute hemorrhagic shock.


METHODS
Forty-eight adult male SD rats were adopted 60-min hemorrhagic shock through removing 30% (5 mL) of the total blood volume, and followed by 2-h resuscitation with shed blood and L-lactated Ringer's solution. At the end of shock and prior to resuscitation, NS, δ(1)-OR agonist TAN-67 (10 mg/kg) and antagonist BNTX (3 mg/kg), and BNTX+TAN-67, DMSO, δ(2)-OR agonist Deltorphin II (1 mg/kg) and antagonist NTB (2 mg/kg), and NTB+Deltorphin II in 0.5 mL were administrated. Left ventricular function parameters were measured during the whole experimental period. Myocardial mitochondria were isolated to determine opening of mitochondrial permeability transition pore (mPTP). Morphologic changes in myocardium and mitochondria were observed by electron microscope.


RESULTS
The hemodynamic indexes in group TAN-67 and group Deltorphin II were higher than control group at each time point during resuscitation, respectively (P<0.05). TAN-67 and Deltorphin II decrease but their antagonists BNTX and NTB increase the opening of mPTP (P<0.05). Myocardial and mitochondrial damage were attenuated in group TAN-67 and group Deltorphin II.


CONCLUSIONS
δ(1)-OR agonist TAN-67 and δ(2)-OR agonist Deltorphin II protect the heart by targeting the mPTP in rats with acute hemorrhagic shock.
Zeng
Xiaoli
X
Department of Anesthesiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Zhao
Xiaoling
X
Yang
Yonghui
Y
Kuai
Jianke
J
Gao
Changjun
C
Yu
Daihua
D
Zhao
Hui
H
Chai
Wei
W
Yao
Linong
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006335:Heart Injuries / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D023421:Models, Animal; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications*
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009842:Oligopeptides; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67; C060209:deltorphin II, Ala(2)-