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 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/microL/g) was greater in NEC-healthy tissue than control or NEC-diseased tissues. The specific iNOS antagonist L-Nomega-(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.
Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, USA. nowickip@pediatrics.ohio-state.edu
Philip T
PT
Nowicki
Kristina M
KM
Reber
Peter J
PJ
Giannone
Craig A
CA
Nankervis
Sue
S
Hammond
Gail E
GE
Besner
Donna A
DA
Caniano
D000818:Animals; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D013223:Statistics as Topic; D013552:Swine
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen