Inhibition of calcium-dependent nitric oxide synthase causes ileitis and leukocytosis in guinea pigs

Digestive Diseases and Sciences
M J MillerD A Clark

Abstract

As nitric oxide reduces gut epithelial permeability, we designed a study to determine if chronic nitric oxide synthase inhibition predisposes the gut to inflammation. Nitric oxide synthase (NOS) inhibitors were administered in the drinking water ad libitum, for seven days: aminoguanidine (10 micrograms/ml), a selective inhibitor of the inducible form of nitric oxide synthase; and NG-nitro-L-arginine methyl ester (L-NAME, 1, 10, and 100 micrograms/ml), which inhibits both the constitutive and inducible forms. Control animals drank tap water only or water with D-NAME, the inactive enantiomer. After one week, circulating leukocyte count and tissue myeloperoxidase activity were measured. L-NAME (100 micrograms/ml), but not D-NAME or aminoguanidine, caused a twofold increase in a circulating leukocyte numbers. This increase in leukocyte numbers was time- and dose-dependent, but the differential count was unaltered. Tissue myeloperoxidase (MPO) activity as an index of granulocyte infiltration was comparable in all groups in the stomach, jejunum, colon, liver, lung, kidney, heart, and skeletal muscle. However, ileal MPO activity was elevated threefold in the L-NAME-(100 micrograms/ml) treated group (P < 0.05). Results in the D-NAME an...Continue Reading

References

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Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P KubesD N Granger
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Jan 1, 1993·Agents and Actions·M J MillerD A Clark
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Citations

Jun 1, 1996·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·M J MillerD A Clark
Jan 1, 1996·Free Radical Biology & Medicine·M J MillerM R Pierce
Jun 28, 2003·The British Journal of Nutrition·Muriel LaraucheJean Fioramonti
Jan 1, 1995·Mediators of Inflammation·M J Miller, M B Grisham
Nov 1, 1994·American Journal of Obstetrics and Gynecology·A L DiketM J Miller
Oct 12, 2000·The Journal of Surgical Research·T C Hua, S M Moochhala
Dec 20, 2014·Nitric Oxide : Biology and Chemistry·Subha Arthur, Uma Sundaram
Dec 22, 2006·The Journal of Nutrition·Alexandr ParlesakLuc Cynober
Oct 1, 1995·Alimentary Pharmacology & Therapeutics·P D ReynoldsJ O Hunter
Dec 21, 2016·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·D F SharradS J H Brookes
Sep 1, 2000·The American Journal of Medicine·P Kubes, D M McCafferty

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