Beneficial Actions of Nalorphine during Hemorrhagic Shock in Cats

Endogenous opiates have been reported to have detrimental effects on the circulatory system during hemorrhagic shock. However, the specific opiate receptor subtype which mediates these actions has not been defined. In the present study, we have utilized the mixed agonist/ antagonist, nalorphine (N-allylnormorphine), which exhibits kappa (κ) and sigma (σ) receptor agonism as well as mu (μ) receptor antagonism, to investigate the role of the mu receptor in hemorrhagic shock. Nalorphine (2 mg/kg) produced no significant changes in any observed experimental variable in sham-shocked animals. Shocked animals treated with nalorphine (2 mg/kg) maintained significantly higher final mean arterial blood pressures (MABP) than animals which received only vehicle (102 ± 3.8 vs 61 ± 6.6 mm Hg, respectively, p < 0.001). In addition, nalorphine significantly reduced the rise in plasma MDF activity observed in untreated hemorrhaged animals (42 ± 3.0 vs 59 ± 4 U/ml, p < 0.02). Our results support a significant role for the mu receptor in the deleterious actions of endogenous opioids during hemorrhagic shock.