Intestinal O₂ consumption in necrotizing enterocolitis: Role of nitric oxide

We tested the hypothesis that inducible isoform of nitric oxide synthase (iNOS)-derived nitric oxide (NO) inhibits oxygen consumption (Vo₂) in human intestine resected for necrotizing enterocolitis (NEC). Each NEC resection specimen was divided into two sections based on histologic appearance: healthy or diseased. Intestine removed from infants for reasons other than NEC was used as control. The tissue injury score (0-6, with 6 indicating complete necrosis) was 0.4 ± 0.2 in control tissue, 1.2 ± 0.4 in NEC-healthy tissue, and 4.6 ± 0.5 in NEC-diseased tissue. Prominent iNOS staining was present in villus enterocytes in NEC-healthy tissue but not in the other tissue types. Intestinal Vo₂ (per direct oximetry, in nM O ₂/min/g) was significantly greater in control tissue than in NEC-healthy or NEC-diseased tissues. Accumulation of NO into buffer bathing intestinal slices (in nM NO/μL/g) was greater in NEC-healthy tissue than control or NEC-diseased tissues. The specific iNOS antagonist L-N ^ω-(1-iminoethyl)-lysine (L-NIL) reduced buffer NO concentration 76% and increased Vo₂ by 90% in NEC-healthy tissue; however, L-NIL had no effect on NO or Vo₂ in control or NEC-diseased tissue. Addition of exogenous NO via S-nitroso-N-acetylpenicillamine depressed Vo ₂ in NEC-healthy and control tissues but not NEC-diseased tissue. A significant correlation was present between buffer NO concentration and Vo ₂ in NEC-healthy tissue. We conclude that iNOS-derived NO suppresses Vo₂ in intestine resected for NEC that demonstrates a relatively normal histology on light microscopy.