TY - JOUR
T1 - Gastrointestinal transit during endotoxemia
T2 - The role of nitric oxide
AU - Wirthlin, Douglas J.
AU - Cullen, Joseph J.
AU - Spates, Stephen T.
AU - Conklin, Jeffrey L.
AU - Murray, Joseph
AU - Caropreso, David K.
AU - Ephgrave, Kimberly S.
N1 - Funding Information:
The authors thank Eugene Clark, Kim Broadhurst, and Marilyn Hinkhouse for technical assistance and Julie Frantz for secretarial assistance. Supported by a Merit Review grant from the Department of Veterans Affairs (J.J.C.).
PY - 1996/2/1
Y1 - 1996/2/1
N2 - We hypothesized that the disrupted gastrointestinal transit that occurs during endotoxemia is mediated by nitric oxide (NO) and that the inhibition of NO synthesis will normalize intestinal transit and gastric emptying. To determine the effects of endotoxin and steroids on the activity of gastrointestinal smooth muscle NO synthase, rats underwent placement of an intravenous (iv) line and then were given Escherichia coli lipopolysaccharide (LPS), 10 mg/kg/iv; LPS, 10 mg/kg/iv + dexamethasone, 3 mg/kg/iv; or saline. The activity of nitric oxide synthase in the stomach, small intestine, and colon were determined by measuring the conversion of L-[3H]arginine to L- [3H]citrulline. To determine intestinal transit and gastric emptying, garage feedings of nonabsorbable liquid markers were given and rats divided into eight groups: 0.9% NaCl, 1 ml/hr x 5 hr (control); LPS, 10 mg/kg/iv; LPS + N(ω)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N(ω)-nitro-D-arginine methyl ester (D-NAME), 10 mg/kg/hr x 5 hr; LPS + L- arginine, 100 mg/kg/hr x 5 hr; LPS + L-NAME + L-arginine; LPS + N(ω)-nitro- L-arginine (L-NNA), 10 mg/kg/hr; or LPS + L-NNA + L-arginine. LPS increased the enzymatic activity of both the constitutive and the inducible forms of NO synthase in the small intestine and fundus of the stomach. The acceleration of intestinal transit produced by endotoxemia was reversed with both L-NAME and L-NNA but not with D-NAME. Endotoxemia slowed gastric emptying but this effect was not reversed with either L-NAME or L-NNA. We conclude that NO plays a major role in mediating the rapid intestinal transit during endotoxemia.
AB - We hypothesized that the disrupted gastrointestinal transit that occurs during endotoxemia is mediated by nitric oxide (NO) and that the inhibition of NO synthesis will normalize intestinal transit and gastric emptying. To determine the effects of endotoxin and steroids on the activity of gastrointestinal smooth muscle NO synthase, rats underwent placement of an intravenous (iv) line and then were given Escherichia coli lipopolysaccharide (LPS), 10 mg/kg/iv; LPS, 10 mg/kg/iv + dexamethasone, 3 mg/kg/iv; or saline. The activity of nitric oxide synthase in the stomach, small intestine, and colon were determined by measuring the conversion of L-[3H]arginine to L- [3H]citrulline. To determine intestinal transit and gastric emptying, garage feedings of nonabsorbable liquid markers were given and rats divided into eight groups: 0.9% NaCl, 1 ml/hr x 5 hr (control); LPS, 10 mg/kg/iv; LPS + N(ω)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N(ω)-nitro-D-arginine methyl ester (D-NAME), 10 mg/kg/hr x 5 hr; LPS + L- arginine, 100 mg/kg/hr x 5 hr; LPS + L-NAME + L-arginine; LPS + N(ω)-nitro- L-arginine (L-NNA), 10 mg/kg/hr; or LPS + L-NNA + L-arginine. LPS increased the enzymatic activity of both the constitutive and the inducible forms of NO synthase in the small intestine and fundus of the stomach. The acceleration of intestinal transit produced by endotoxemia was reversed with both L-NAME and L-NNA but not with D-NAME. Endotoxemia slowed gastric emptying but this effect was not reversed with either L-NAME or L-NNA. We conclude that NO plays a major role in mediating the rapid intestinal transit during endotoxemia.
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U2 - 10.1006/jsre.1996.0048
DO - 10.1006/jsre.1996.0048
M3 - Article
C2 - 8598659
AN - SCOPUS:0030025860
SN - 0022-4804
VL - 60
SP - 307
EP - 311
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -