ENDOTOXIN ENHANCES NOREPINEPHRINE RELEASE IN THE RAT BY PERIPHERAL MECHANISMS

The study was designed to investigate the effects of endotoxin adminis tration on norepinephrine release in vivo in the rat. The norepinephri ne release rate was calculated from the steady-state concentration of endogenous norepinephrine and [H-3]norepinephrine in the central venou s pool after infusion of [H-3]norepinephrine intra-arterially. This me thod corrects for both metabolism and disposition as the infused trace r closely follows the normal pathway of neuronally released norepineph rine. 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 o f bacterial endotoxin (10 mg/kg intravenously) or an equal volume of s aline (vehicle). Plasma levels of norepinephrine and epinephrine incre ased significantly in both anesthetized and pithed preparations after endotoxin, whereas plasma norepinephrine clearance decreased only in a nesthetized rats. Norepinephrine release rates were significantly incr eased in anesthetized as well as in pithed rat preparations after endo toxin. Plasma epinephrine was elevated more in pithed than anesthetize d rats. The blood pressure fall was more rapid in pithed compared to a nesthetized rats following endotoxin, which probably indicates that th e 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 nor epinephrine release rates induced by bacterial endotoxin in pithed rat s with constant frequency sympathetic nerve stimulation suggests that some factor in endotoxicosis enhances the release of norepinephrine by an action at peripheral nerve terminals. Elevated plasma levels of ep inephrine under similar conditions suggests augmented release from the adrenal medulla during endotoxicosis is also due to a local action.