title: Adrenalectomy blocks pressor responses to naloxone in endotoxic shock: evidence for sympathomedullary involvement.
abstract: The effects of naloxone on endotoxic hypotension in adrenalectomized and selectively adrenal demedullated rats were evaluated. In sham-operated rats, naloxone administered intracerebroventricularly (ICV) and intravenously (IV) produced an elevation of arterial pressure in this conscious rat model of endotoxemia. By contrast, both adrenalectomy and selective adrenal demedullation (wherein cortical function remained) not only enhanced the sensitivity to endotoxin-induced hypotension at least 10- to 15-fold, but also completely prevented the pressor response to ICV or IV naloxone. These results indicate that 1) adrenal enkephalins are probably not the endogenous opiates responsible for shock hypotension since their removal enhances shock susceptibility; 2) pituitary-derived endorphins in the circulation also appear to be uninvolved since naloxone fails to reverse shock hypotension despite reported elevations of circulating beta-endorphin in adrenalectomized rats; 3) since evidence indicates that naloxone acts centrally in intact endotoxemic rats and fails to do so following adrenal demedullation, we suggest that endotoxic shock results in an endogenous opiate inhibition of central autonomic sites regulating sympatho-medullary outflow. Naloxone, by reversing these actions, may result in the increased release of pressor substances from the adrenal medulla.
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004723:Endorphins / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology; D012772:Shock, Septic / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D004723:Endorphins; D011957:Receptors, Opioid; D009270:Naloxone