PERIPHERAL ENDOTOXIN INCREASES SPLENIC SYMPATHETIC-NERVE ACTIVITY VIACENTRAL PROSTAGLANDIN SYNTHESIS

We tested whether prostaglandin synthesis mediates the lipopolysacchar ide (LPS)induced increase in splenic sympathetic nerve activity. Sprag ue-Dawley rats were pretreated with intravenous or intracerebroventric ular injections of indomethacin, and splenic nerve activity was record ed after intravenous injections of LPS. In vehicle-pretreated rats, 10 0 mu g LPS induced a 62.8 +/- 5.6% increase in splenic nerve activity beginning 22.7 +/- 2.7 min postinjection. All vehicle-pretreated anima ls responded to high (100 mu g, 5 of 5 animals) and low (10 mu g, 8 of 8 animals) doses of LPS. Both intravenous (15 mg/kg) and intracerebro ventricular (50 mu g) pretreatments with indomethacin delayed (F-1,F-1 9 = 30.66, P < 0.001) the increase in nerve activity after 100 mu g LP S. When given intravenously, 50 mu g indomethacin (the intracerebroven tricular dose) did not delay the response to intravenous LPS, indicati ng that the effects of intracerebroventricular indomethacin pretreatme nt were restricted to the central nervous system. Importantly, intrace rebroventricular indomethacin reduced (2 of 7 animals) or completely b locked (5 of 7 animals) the splenic nerve response to the low dose of LPS (10 mu g, iv). The indomethacin effects could not be accounted for by central release of vasopressin because intracerebroventricular inj ection of indomethacin did not alter baseline nerve activity or blood pressure, whereas intracerebroventricular injection of vasopressin rap idly increased both measures. Additionally, central injection of LPS d id not elevate splenic nerve activity, whereas intracerebroventricular injection of prostaglandin E-2 induced a rapid (2.2 +/- 2.7 min) incr ease in splenic nerve activity. These data indicate that central prost aglandin synthesis is an intermediate step whereby systemic LPS elicit s an increase in sympathetic outflow to an immune organ.