Prophylactic administration of L-arginine improves the intestinal barrier function after mesenteric ischaemia.
BACKGROUND
Ischaemia/reperfusion (I/R) of the intestine causes mucosal injury associated with a high death rate in rats.


OBJECTIVE
To investigate whether nitric oxide (NO) might be implicated in the recovery of the intestinal mucosa after ischaemic insult.


METHODS
Wistar rats were subjected to mesenteric artery occlusion for 90 minutes. The animals were given either L-arginine, the substrate of NO synthase, or molsidomine, a NO donor. The controls received casein hydrolysate. The compounds were administered by gavage 19, 16, and 1.5 hours before ischaemia. Mucosal barrier permeability and cGMP content were determined 24 hours after ischaemia.


RESULTS
Survival after I/R was 50% in the control group. Animals treated with L-arginine or molsidomine exhibited a higher survival rate (70% and 83% respectively). Mucosal barrier permeability was decreased in rats receiving L-arginine or molsidomine compared with controls (4.0 (0.9) and 2.6 (0.6) v 11.2 (1.6) 14C-PEG pmol/segment, p < 0.05). Increased cGMP content was seen in the mucosa of the L-arginine group.


CONCLUSIONS
The findings suggest that pretreatment with L-arginine or molsidomine ameliorates survival after intestinal I/R and improves mucosal barrier function.
Schleiffer
R
R
Institut de Recherche sur les Cancers de I'Appareil Digestif (IRCAD), Hôpitaux Universitaires, Strasbourg, France.
Raul
F
F
D000601:Amino Acids, Essential / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000032:analysis; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries; D008981:Molsidomine / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010539:Permeability; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
D000601:Amino Acids, Essential; D014665:Vasodilator Agents; D011092:Polyethylene Glycols; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP