Opioid δ 1 and δ 2 Receptor Agonist Attenuate Myocardial Injury Via mPTP in Rats With Acute Hemorrhagic Shock

Abstract

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. 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. 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. 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.