Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock

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IT is known that the cardiovascular system is extremely sensitive to the effects of both exogenous1,2 and endogenous3 opiates. In rats, less than 1% of the morphine dose necessary to produce antinociception results in significant hypotension and brady-cardia4. The endogenous opiate β-endorphin is stored along with pituitary adrenocorticotrophin (ACTH)5,6, and the action of stressors seems to result in the release of both peptides5,6. Therefore, it seemed likely that β-endorphin is released during shock states and that it might contribute to the hypotension. To test this hypothesis we used an endotoxin shock model7,8. If endotoxin-induced hypotension were mediated through endorphin release, then blockade of endorphins should reverse such hypotension. Using the specific opiate antagonist, naloxone, we not only rapidly reversed endotoxin-induced hypotension, but also prophylactically blocked its occurrence. These findings suggest that endorphins may have a role in the patho-physiology of shock and that narcotic antagonists should be evaluated for their potential therapeutic value in the treatment of shock.

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HOLADAY, J., FADEN, A. Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature 275, 450–451 (1978) doi:10.1038/275450a0

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