The present available
opioid receptor antagonists such as
naloxone and
naltrexone are not highly receptor selective. They may antagonize
mu opioid receptors to affect the pain threshold of the patients with
traumatic shock while they exert antishock effects. Therefore, they are not suitable for
traumatic shock. It is very important to elucidate the subclass of
opioid receptors that are closely associated with cardiovascular depression of
traumatic shock and then choose their specific receptor antagonists to treat it.
Traumatic shock was used in
pentobarbital-anesthetized Wistar rats by right femur fracture plus
hemorrhage (fixed
hemorrhage at a rate of 20 mL/kg in experiment 1 or
hemorrhage to 40 mmHg mean arterial blood pressure for 60 min in experiments 2 and 3), and the changes of myocardial and brain
opioid receptors after
traumatic shock, the antagonizing effects of mu, delta, and
kappa opioid receptor antagonists on the cardiovascular depression of
traumatic shock and the antishock effects of delta and
kappa opioid receptor antagonists ICI174,864 and
Nor-binaltorphimine (
Nor-BNI) were observed. The results indicate that after
traumatic shock, the number of myocardial and brain delta and
kappa opioid receptors were significantly increased that were significantly associated with the decreased cardiovascular functions.
mu Opioid receptors in the heart and brain did not change significantly. Intracerebral ventricular administration of ICI174,864 and
Nor-BNI significantly antagonized the decreased cardiovascular function after
traumatic shock and increased the survival rate of
traumatic shock rats, but
mu opioid receptor antagonist
beta-funaltrexamine did not. Meanwhile,
intravenous administration of delta and
kappa opioid receptor antagonists ICI174,864 and
Nor-BNI also significantly increased the mean arterial blood pressure, improved the hemodynamic parameters, and prolonged the survival rate of
traumatic shock rats. These findings suggest that
opioid receptors are involved in the cardiovascular depression of
traumatic shock, and the subclass receptors are mainly delta and
kappa opioid receptors. delta and
kappa opioid receptor antagonists have good beneficial effects on
traumatic shock.