Captopril reduces the severity of bowel damage in a neonatal rat model of necrotizing enterocolitis.
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.
Zani
Augusto
A
Department of Paediatric Surgery, Institute of Child Health, WC1N 1EH London, UK.
Eaton
Simon
S
Leon
Francesco Fascetti
FF
Malerba
Alberto
A
Hall
Nigel J
NJ
De Coppi
Paolo
P
Smith
Virpi V
VV
Pierro
Agostino
A
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
D002216:Captopril