The effects of δ,κ opioid receptor antagonists on traumatic hemorrhagic shock

Objective:To elucidate opioid receptor subtypes associated with traumatic hemorrhagic shock and study beneficial effects of their antagonists on traumatic hemorrhagic shock.Methods:Traumatic hemorrhagic shock models were duplicated in rabbits and rats.Experiments were carried out in rabbits in 2 parts.In part I,the relationship between plasma βendorphin (βEP) and mean arterial pressure (MAP),hemodynamic parameters of shock were observed.In part Ⅱ,experiment was performed to observe the effects of intracerebroventricular injection of anti βEP serum,δopioid receptor antagonistICI174864 and κopioid receptor antagonistNorBNI on hemodynamic parameters,LDH and βG.In shock rats,the effects of ICI174864 and NorBNI on hemodynamic,survival time and 5hour survival rate were also determined.Results:It was shown that plasma βEP sharply increased following traumatic hemorrhagic shock,but MAP,hemodynamic parameters notably decreased,and they were negatively correlated.Intracerebroventricular treatment with anti βEP serum could reverse above changes in rabbits,and ICI174864 and NorBNI effectively controlled traumatic hemorrhagic shcok both in rabbits and rats.After administration of these receptor antagonists,MAP and hemodynamics markedly improved,plasma LDH and βG levels decreased,and survival time as well as 5hour survival rate enhanced.Conclusions:βEP appears to be involved in the pathogenesis of traumatic hemorrhagic shock mediated by δ and κ opioid receptors.δ and κ opioid receptor antagonists would hopefully be new drugs in the treatment of traumatic and hemorrhagic shock.