NALOXONE TREATMENT OF ENDOTOXIN-SHOCK - STEREOSPECIFICITY OF PHYSIOLOGIC AND PHARMACOLOGIC EFFECTS IN THE RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 212  (3) , 441-447
Abstract
Endogenous opiates (endorphins; EPs) like exogenous opiates can, even in small doses, profoundly depress blood pressure [BP] and heart rate. Since EP are released in response to stressors, it appeared possible that EP might be released during shock and serve to further reduce BP. The specific opiate-antagonist naloxone [NX] was used to block these anticipated effects of EP in a conscious rat endotoxin-shock model. NX treatment resulted in a rapid increase in mean arterial pressure (MAP) in animals made hypotensive by Escherichia coli endotoxin administration. NX was effective in reversing this hypotension at a dose as small as 0.1 mg/kg. This therapeutic effect of NX was stereospecific: (-)-NX reversed the hypotension, although its stereoisomer (+)-NX did not. A single 10 mg/kg i.v. bolus injection of NX significantly improved MAP for a period of 30 min, and MAP remained elevated as compared to saline controls for approximately 2 h. Bolus injections of NX followed by continuous i.v. infusion produced similar changes in MAP. Despite the rapid effect of NX in restoring MAP toward base-line levels, 24-h survival was not significantly improved by this narcotic antagonist. Factors other than hypotension are apparently critical determinants of survival in this rat model. These findings support the hypothesis that EPs are hypotensive factors in endotoxin shock and suggest that the therapeutic effects of NX are specific and are mediated by the opiate receptor.