Gastric stasis in neuronal nitric oxide synthase-deficient knockout mice.
OBJECTIVE
Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut. This study aimed to identify the effect of chronic deprivation of NO derived from neuronal (nNOS) or endothelial (eNOS) nitric oxide synthase on gastric emptying.


METHODS
nNOS-deficient (knockout) mice were compared with wild-type mice for gastric size, fluoroscopic appearance after gavage of contrast, and histology of the pyloric sphincter. Wild-type mice treated with the NOS inhibitor N(omega)-nitro L-arginine (L-NA) and eNOS-deficient mice were also compared with wild-type and nNOS-deficient mice for liquid and solid gastric emptying.


RESULTS
nNOS-deficient mice showed gastric dilation. Fluoroscopy showed delayed gastric emptying of radiologic contrast. There was no marked localized hypertrophy or luminal narrowing at the pyloric sphincter by histology of relaxed wild-type, nNOS-deficient, and eNOS-deficient tissues. Gastric emptying of both solids (28% +/- 27%) and liquids (22% +/- 18%) was significantly delayed in nNOS-deficient mice compared with control wild-type mice (82% +/- 22% for solids; 48% +/- 17% for liquids). eNOS-deficient mice showed no significant difference from wild-type mice (74% +/- 28% for solids; 47% +/- 23% for liquids). Wild-type mice treated acutely with L-NA showed delay in emptying of solids (43% +/- 31%) but not liquids (39% +/- 15%).


CONCLUSIONS
Chronic depletion of NO from nNOS, but not eNOS, results in delayed gastric emptying of solids and liquids.
Mashimo
H
H
West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts 02132, USA. mashimo@helix.mgh.harvard.edu
Kjellin
A
A
Goyal
R K
RK
D000818:Animals; D015153:Blotting, Western; D005746:Gastric Emptying / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012016:Reference Values; D013270:Stomach / Q000201:enzymology / Q000473:pathology
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse