Cardiac and splenic norepinephrine turnovers in endotoxic rats

Although sympathetic hyperactivity has been implicated in the pathogenesis of endotoxin shock, methodologies employed to assess the activity have been indirect in nature and results have been equivocal. The present experiments quantitated postganglionic sympathetic activity by measuring norepinephrine (NE) turnovers in hearts and spleens of fasted male Holtzman rats injected intravenously with Salmonella enteritidis lipopolysaccharide (2 mg/300 g rat; 5.7-6.7 mg/kg). NE turnovers were measured over 12 h by the [3H]NE decay method. Cardiac NE turnovers were increased in endotoxic rats (0.075 micrograms X g-1 X h-1) compared with controls (0.009). Similarly, NE turnovers in spleens of endotoxic rats (0.099 micrograms X g-1 X h-1) were increased compared with control rats (0.033). Because NE reuptake is depressed in spleens of severely shocked endotoxic rats, the singular effect of reduced reuptake (desmethylimipramine treatment, 20 mg/kg) on NE turnovers was evaluated in spleens of a separate group of control rats. Desmethylimipramine had no effect on the slopes of the NE decay lines compared with untreated rats (-0.015 +/- 0.008 vs. -0.015 +/- 0.029, respectively). Thus these experiments support the concept of heightened sympathetic activation during endotoxicosis as assessed quantitatively in a noninvasive, unanesthetized rat model.