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Endotoxin enhances norepinephrine release in the rat by peripheral mechanisms.

The study was designed to investigate the effects of endotoxin administration on norepinephrine release in vivo in the rat. The norepinephrine release rate was calculated from the steady-state concentration of endogenous norepinephrine and [3H]norepinephrine in the central venous pool after infusion of [3H]norepinephrine intra-arterially. This method corrects for both metabolism and disposition as the infused tracer closely follows the normal pathway of neuronally released norepinephrine. Measurements were made in anesthetized intact rats as well as in pithed rats with electrically stimulated sympathetic outflow (3 Hz). Comparisons were made before and for 60 min following administration of bacterial endotoxin (10 mg/kg intravenously) or an equal volume of saline (vehicle). Plasma levels of norepinephrine and epinephrine increased significantly in both anesthetized and pithed preparations after endotoxin, whereas plasma norepinephrine clearance decreased only in anesthetized rats. Norepinephrine release rates were significantly increased in anesthetized as well as in pithed rat preparations after endotoxin. Plasma epinephrine was elevated more in pithed than anesthetized rats. The blood pressure fall was more rapid in pithed compared to anesthetized rats following endotoxin, which probably indicates that the central nervous system is able to compensate to some extent for the blood pressure fall in the anesthetized rat. Heart rate was unchanged in both preparations following endotoxin. Significant increases in norepinephrine release rates induced by bacterial endotoxin in pithed rats with constant frequency sympathetic nerve stimulation suggests that some factor in endotoxicosis enhances the release of norepinephrine by an action at peripheral nerve terminals.