Subclass opioid receptors associated with the cardiovascular depression after traumatic shock and the antishock effects of its specific receptor antagonists.
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.
Liu
Liang-ming
LM
State Key Laboratory of Trauma, Burns, and Combined Injury, The Second Department of Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, People's Republic of China. liulmh@online.cq.cn
Hu
De-yao
DY
Pan
Xue-kun
XK
Lu
Ru-quan
RQ
Dan
Fei-jun
FJ
D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000473:pathology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005269:Femur / Q000473:pathology; D005609:Free Radicals; D018757:GABA Modulators / Q000494:pharmacology; D006439:Hemodynamics; D015233:Models, Statistical; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012769:Shock / Q000473:pathology*; D013997:Time Factors
D005609:Free Radicals; D018757:GABA Modulators; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D010424:Pentobarbital