Mu-opioid receptor blockade protects against circulatory shock and cerebral ischemia during heatstroke.
Naltrexone, a nonselective antagonist of opioid receptors, is found to be beneficial in protecting against heatstroke. Further investigation using selective mu, delta, and kappa opioid receptor antagonists are needed to prove the involvement of specific receptors in heatstroke. Rats under sodium pentobarbital anesthesia were exposed to high ambient temperature of 43 degrees C to induce heatstroke. Control rats were exposed to 24 degrees C. In rats treated with normal saline 20 minutes before heat stress, the values for survival time were found to be 89-101 minutes. Intravenous administration of CTAP (a selective mu-opioid receptor antagonist; 50-200 microg/kg), but not nor-binaltorphimine (20-200 microg/kg; a kappa-opioid receptor antagonist) or ICI-174864 (50-500 microg/kg; a delta-opioid receptor antagonist), significantly increased the survival time to new values of 180-212 minutes. In vehicle-treated rats after heatstroke onset, the values for core temperature, intracranial pressure, and the extracellular markers for ischemia (eg, glutamate and lactate/pyruvate ratio) or damage (eg, glycerol) and neuronal damage scores in striatum were significantly higher than those of normothermic controls. In contrast, the values for mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of O2 were significantly lower than those of normothermic controls. The heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral hypoperfusion and hypoxia, and increased levels of cellular ischemia and damage markers in striatum were all significantly attenuated by prior administration of CTAP. The data indicate that prior antagonism of mu-opioid receptors protects against circulatory shock and cerebral ischemia during heatstroke.
Chen
Zhih-Cherng
ZC
Department of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan.
Kuo
Jinn-Rung
JR
Huang
Yi-Ping
YP
Lin
Mao-Tsun
MT
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D018883:Heat Stroke / Q000188:drug therapy* / Q000473:pathology; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009474:Neurons / Q000473:pathology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012769:Shock / Q000517:prevention & control*; D013004:Somatostatin
C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D017450:Receptors, Opioid, mu; D013004:Somatostatin