title: Captopril reduces the severity of bowel damage in a neonatal rat model of necrotizing enterocolitis.
abstract: OBJECTIVE
  Selective mesenteric ischemia may result from activation of the renin-angiotensin system during periods of shock and is implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC). We investigated the effectiveness of captopril, an angiotensin-converting enzyme inhibitor, in reducing the severity of bowel damage in a neonatal rat model of NEC.
  
  
  METHODS
  Necrotizing enterocolitis was induced by a combination of gavage feeding of hypertonic formula, hypoxia, and oral lipopolysaccharide (LPS). Rats were randomly divided into 3 groups: group A, control (breast fed; n = 20); group B, NEC (gavage/hypoxia/LPS; n = 31); group C, NEC with captopril 20 mg/kg per dose with the formula for 4 days (gavage/hypoxia/LPS/captopril; n = 35). Pups were killed after 4 days. Incidence of NEC was evaluated microscopically.
  
  
  RESULTS
  Severity of bowel damage was higher in the NEC group compared to controls and was reduced by administration of captopril. Dilatation of the intestinal vasculature was observed in the captopril group. There were no cases of NEC in the controls; the incidence increased to 55% in NEC group and reduced to 29% by captopril.
  
  
  CONCLUSIONS
  In this model of neonatal NEC, captopril supplementation of formula reduces the severity of intestinal damage and the incidence of NEC, presumably by affecting mesenteric blood flow.
authors.affiliation: Department of Paediatric Surgery, Institute of Child Health, WC1N 1EH London, UK.
authors.forename: Augusto
authors.initials: A
authors.lastname: Zani
authors.forename: Simon
authors.initials: S
authors.lastname: Eaton
authors.forename: Francesco Fascetti
authors.initials: FF
authors.lastname: Leon
authors.forename: Alberto
authors.initials: A
authors.lastname: Malerba
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Hall
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.forename: Virpi V
authors.initials: VV
authors.lastname: Smith
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D007082:Ileum / Q000187:drug effects* / Q000473:pathology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D013152:Splanchnic Circulation / Q000187:drug effects*; D015996:Survival Rate
chemical_list: D002216:Captopril