Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesis.
We tested whether prostaglandin synthesis mediates the lipopolysaccharide (LPS)-induced increase in splenic sympathetic nerve activity. Sprague-Dawley rats were pretreated with intravenous or intracerebroventricular injections of indomethacin, and splenic nerve activity was recorded after intravenous injections of LPS. In vehicle-pretreated rats, 100 micrograms LPS induced a 62.8 +/- 5.6% increase in splenic nerve activity beginning 22.7 +/- 2.7 min postinjection. All vehicle-pretreated animals responded to high (100 micrograms, 5 of 5 animals) and low (10 micrograms, 8 of 8 animals) doses of LPS. Both intravenous (15 mg/kg) and intracerebroventricular (50 micrograms) pretreatments with indomethacin delayed (F1.19 = 30.66, P < 0.001) the increase in nerve activity after 100 micrograms LPS. When given intravenously, 50 micrograms indomethacin (the intracerebroventricular dose) did not delay the response to intravenous LPS, indicating that the effects of intracerebroventricular indomethacin pretreatment were restricted to the central nervous system. Importantly, intracerebroventricular indomethacin reduced (2 of 7 animals) or completely blocked (5 of 7 animals) the splenic nerve response to the low dose of LPS (10 micrograms, iv). The indomethacin effects could not be accounted for by central release of vasopressin because intracerebroventricular injection of indomethacin did not alter baseline nerve activity or blood pressure, whereas intracerebroventricular injection of vasopressin rapidly increased both measures. Additionally, central injection of LPS did not elevate splenic nerve activity, whereas intracerebroventricular injection of prostaglandin E2 induced a rapid (2.2 +/- 2.7 min) increase in splenic nerve activity. These data indicate that central prostaglandin synthesis is an intermediate step whereby systemic LPS elicits an increase in sympathetic outflow to an immune organ.
MacNeil
B J
BJ
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Jansen
A H
AH
Janz
L J
LJ
Greenberg
A H
AH
Nance
D M
DM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004594:Electrophysiology; D004731:Endotoxins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D011453:Prostaglandins; D007213:Indomethacin