Abstract
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 O2/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-Nω-(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 Vo2 in NEC-healthy and control tissues but not NEC-diseased tissue. A significant correlation was present between buffer NO concentration and Vo2 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.
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Abbreviations
- DNP:
-
2,4-dinitrophenol
- eNOS:
-
endothelial nitric oxide synthase
- l-NIL:
-
l-Nω-(1-iminoethyl)-lysine
- l-NNA:
-
l-NG-nitroarginine
- NEC:
-
necrotizing enterocolitis
- SNAP:
-
S-nitroso-N-acetylpenicillamine
- SP:
-
substance P
- Vo2:
-
oxygen consumption
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This work was funded by National Institutes of Health Grant DK 065306 (P.T.N.)
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Nowicki, P., Reber, K., Giannone, P. et al. Intestinal O2 Consumption in Necrotizing Enterocolitis: Role of Nitric Oxide. Pediatr Res 59, 500–505 (2006). https://doi.org/10.1203/01.pdr.0000203094.27615.5f
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DOI: https://doi.org/10.1203/01.pdr.0000203094.27615.5f
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