The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats.
OBJECTIVE
Nitric oxide is an endothelium-derived relaxing factor that promotes capillary integrity, inhibits leukocyte adherence and activation, and scavenges oxygen radicals. Because these effects are important in experimental intestinal injury, we studied the role of NO inhibition on hypoxia-induced bowel necrosis in the rat and investigated the interaction between platelet-activating factor (PAF) and NO in this model.


METHODS
Sprague-Dawley rats were treated with either hypoxia, NO synthase inhibition (NG-methyl-L-arginine [LNMA] or NG-nitro-L-arginine methyl ester [L-NAME]), hypoxia+LNMA, hypoxia+LNMA+NO donors, or hypoxia+LNMA+PAF receptor inhibition. Evaluations included blood pressure, superior mesenteric artery blood flow, arterial blood gases, histological intestinal injury, intestinal myeloperoxidase activity, and intestinal PAF activity.


RESULTS
We found that hypoxia alone for 90 minutes (10% O2, partial O2 pressure = 45 mm Hg) or LNMA alone had no detrimental effects. However, hypoxia+LNMA together caused hypotension, metabolic acidosis, intestinal injury, increased intestinal myeloperoxidase activity, and elevated intestinal PAF concentrations that were prevented by exogenous L-arginine. Furthermore, the hypotension and intestinal injury was prevented by PAF receptor blockade.


CONCLUSIONS
We conclude that endogenous NO protects the intestine from hypoxia-induced inflammation and injury, and the balance between local PAF and NO modulates the outcome of hypoxia-stressed intestine.
Caplan
M S
MS
Department of Pediatrics, Evanston Hospital, Illinois.
Hedlund
E
E
Hill
N
N
MacKendrick
W
W
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology*; D007422:Intestines / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine
D010972:Platelet Activating Factor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester