Pharmacological characterization of nitric oxide production in a rat model of meningitis.
Depending on its concentration and target site, nitric oxide (NO) is an intracellular messenger or inflammatory mediator. Recent research supports an expanded role for NO in the pathophysiology of neuroinflammatory diseases. Using analytical and pharmacological techniques, the present study identifies NO as a potential inflammatory mediator in experimental meningitis in the rat. Intracisternal administration of lipopolysaccharide (LPS) induced NO synthesis from the lateral and third ventricle choroid plexi and surface meninges but not from systemic white blood cells, suggesting that meningeal inflammation was restricted to the central nervous system. The time course of NO production revealed at 3 hr lag after intracisternal LPS, followed by a peak of 8 hr and subsequent decrease to baseline 24 hr after LPS dosing. The pharmacological rank order of NO synthase inhibitors in meningeal preparations (NG-aminoarginine > NG-methylarginine approximately aminoguanidine) was slightly different than the rank order for the LPS-stimulated monocyte-macrophage cell line, J774A.1 (NG-aminoarginine approximately NG-methylarginine > aminoguanidine). A prolonged inhibition of NO production was observed in cultured meningeal preparations or J774A.1 cells briefly exposed to and washed free from NO synthase inhibitors. These findings implicate NO as an inflammatory mediator during experimental meningitis, and suggest that NO synthase inhibitors might be potentially useful agents for meningeal inflammation.
Korytko
P J
PJ
Department of Pharmaceutics, School of Pharmacy, University of Buffalo, NY 14260, USA.
Boje
K M
KM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D004926:Escherichia coli; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008578:Meninges / Q000378:metabolism*; D008581:Meningitis / Q000139:chemically induced / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008070:Lipopolysaccharides; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C063904:N(G)-aminoarginine; D001120:Arginine; D019001:Nitric Oxide Synthase