title: [Study of L-NAME treatment on experimental autoimmune myocarditis].
abstract: OBJECTIVE
  To observe the therapeutic effect of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, on experimental autoimmune myocarditis (EAM) in Balb/C mice and discuss the therapeutic mechanism induced by apoptosis.
  
  
  METHODS
  Thirty male Balb/C mice were divided into normal control group, model control group and experimental group randomly (n = 10). Model control group and experimental group were created into EAM by injection of porcine cardiac myosin subcutaneously in double groin and axilla and pertussis toxin intraperitoneally on day 0 and 7 respectively. Model control group was intraperitoneally administered 5 mg/(kg x day) of physiological saline after infective myosin and pertussis toxin. Experimental group was intraperitoneally given 5 mg/(kg x day) of L-NAME on day 1-21. The hearts and blood were processed after sacrificed on day 21. Cardiac inflammation score was measured by HE staining. Heart weight / body weight (HW/BW), serum nitric oxide (NO) level, activity of induced nitric oxide synthase (iNOS) and mRNA expression of iNOS in heart were measured in each group. Degree of heart apoptosis were evaluated by cardiac apoptotic index through TUNEL, immunohistochemical examination and real time PCR of Caspase-3, Caspase-8 and Caspase-9.
  
  
  RESULTS
  Compared with normal control group, cardiac inflammation score, HW/BW level of NO and activity of iNOS, mRNA expression of iNOS, the levels of mRNA and protein of Caspase-3, Caspase-8 and Caspase-9 and cardiac apoptotic index were significantly higher (P < 0.01) in model control group, and those of model control group were higher than those of experimental group (P < 0.01). HW/BW was only a little elevation in model control group compared with that in the experiment group (P < 0.05).
  
  
  CONCLUSIONS
  The development of EAM is related with the NO catalyzed by iNOS. L-NAME protects cardiac myocyte via suppressing the activity of iNOS and further decreased production of NO in EAM. The mechanism might be that L-NAME alleviated myocardial inflammation through inhibited the apoptosis of cardiac myocyte.
authors.affiliation: The First Department of Cardiovascular Internal Medicine of South Building, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Guo-Lei
authors.initials: GL
authors.lastname: Ding
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Han
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Wang
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.forename: Xiao
authors.initials: X
authors.lastname: Zou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D019331:NG-Nitroarginine Methyl Ester