Inducible nitric oxide synthase inhibitors ameliorate hypermotility observed after T. spiralis infection in the rat.
Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility and hypersecretion. Our aim was to use this experimental model to elucidate if iNOS was involved in the development of gastrointestinal hypermotility. Rats infected with Trichinella spiralis were treated for 4 days with the nitric oxide synthase inhibitors L-NAME or L-NIL. Treatment began either simultaneously with the infection or 3 days after infection when inflammation was already fully developed. In all cases, at day 10-12 after infection, anesthetized rats were prepared with strain gauges and electrodes in the small intestine to evaluate motor activity of the small intestine. In addition, histology and iNOS immunohistochemistry studies were performed. The results showed that both NOS inhibitors blocked iNOS expression in the intestine. None of the NOS inhibitors attenuated the inflammatory process. However, the preventive treatment with L-NIL reversed hypermotility. In contrast, the treatment with NOS inhibitors 3 days after infection was not so effective in reversing motor alterations. L-NAME, but not L-NIL, caused alterations on spontaneous motility. In conclusion, these results indicate that iNOS participates in the development of motor hypermotility in the gut.
Torrents
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D
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Spain.
Prats
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N
Vergara
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P
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000503:physiopathology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017160:Trichinella spiralis / Q000302:isolation & purification*; D014235:Trichinellosis / Q000188:drug therapy* / Q000503:physiopathology
D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester