Gastrointestinal transit during endotoxemia: the role of nitric oxide.
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, gavage 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-omega-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N-omega-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-omega-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.
Wirthlin
D J
DJ
Department of Surgery, University of Iowa College of Medicine, Iowa City, 52242, USA.
Cullen
J J
JJ
Spates
S T
ST
Conklin
J L
JL
Murray
J
J
Caropreso
D K
DK
Ephgrave
K S
KS
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase