title: Effects of oral L-NAME during Trichinella spiralis infection in rats.
abstract: We investigated the involvement of nitric oxide in transmural jejunal alterations induced by Trichinella spiralis (T. spiralis) infection in rats. Rats were gavaged with either saline or T.spiralis larvae, and, 1 h later, rats were treated orally with water, NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), or NG-nitro-D-arginine methyl ester (D-NAME; 30 mg/kg) on a daily basis. Although not observed in jejunum from uninfected rats, inducible nitric oxide synthase (iNOS) mRNA was present in the mucosa and neuromuscular layers of jejunum from T. spiralis-infected rats. On day 6, T. spiralis-infected rats had a 6-fold decrease in transmural nitric oxide synthase activity, an 11-fold increase in plasma nitrite, and a 7-fold elevation in transmural myeloperoxidase (MPO) activity compared with uninfected controls. Intestinal smooth muscle cell hyperplasia and hypertrophy were only detected in the infected rats. L-NAME, but not D-NAME, treatment of infected rats for 6 days caused a pronounced increase in transmural iNOS mRNA expression, coinciding with significantly increased mucosal nitric oxide synthase activity. T. spiralis numbers in L-NAME-treated rats were significantly lower compared with the other two infected groups although L-NAME had no direct effect on T. spiralis viability in vitro. Furthermore, L-NAME treatment significantly reduced plasma nitrite and jejunal MPO but not intestinal smooth muscle cell hyperplasia or hypertrophy. In contrast, D-NAME treatment of infected rats significantly enhanced intestinal smooth muscle hyperplasia and hypertrophy. Taken together, these results suggest that alterations in the T. spiralis-infected jejunum are mediated, in part, by a suppression of nitric oxide synthase activity in the inflamed jejunum.
authors.affiliation: Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: S M
authors.initials: SM
authors.lastname: Collins
authors.forename: M G
authors.initials: MG
authors.lastname: Blennerhassett
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D004790:Enzyme Induction; D007583:Jejunum / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D007814:Larva / Q000187:drug effects; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D009573:Nitrites / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014158:Transcription, Genetic / Q000187:drug effects; D017160:Trichinella spiralis / Q000302:isolation & purification; D014235:Trichinellosis / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology
chemical_list: D015335:Molecular Probes; D009573:Nitrites; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester