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Am J Physiol Gastrointest Liver Physiol (November 18, 2004). doi:10.1152/ajpgi.00327.2004
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Submitted on July 22, 2004
Accepted on November 9, 2004

INFLAMMATION INDUCED CHANGES IN ARACHIDONIC ACID METABOLISM IN CAT LES CIRCULAR MUSCLE

Ling Cheng1, Weibiao Cao1, Jose Behar1, Piero Biancani1, and Karen M. Harnett1*

1 Department of Medicine, Rhode Island Hospital and Brown University, Providence, Rhode Island, USA

* To whom correspondence should be addressed. E-mail: Karen_Harnett{at}Brown.edu.

Myogenic LES tone is maintained by arachidonic acid metabolites, such as PGF2{alpha} and thromboxane A2/B2. Experimental esophagitis in cat reduces LES in vivo pressure and in vitro tone. Because IL-1{beta} may mediate esophagitis-associated reduction in ACh release in esophagus we examined whether IL-1{beta} may also play a role in esophagitis-induced reduction of LES tone. A cat model of experimental esophagitis was obtained by repeated esophageal perfusion with HCl (2, 57). LES circular muscle strips were examined in muscle chambers as previously described (3). Levels of inflammatory mediators were measured. IL-1{beta} levels were higher in esophagitis than in normal LES. IL-1{beta} reduced normal LES tone and the reduction was reversed by catalase, suggesting a role of H2O2 . This was confirmed by IL-1{beta} -induced production of H2O2 in normal LES and elevated H2O2 levels in esophagitis. H2O2 by itself is sufficient to explain the changes that occur in the muscle, reducing its ability to contract. H2O2 increased PGE2 in normal LES and PGE2 levels were elevated in esophagitis LES, PGF2{alpha} levels were unchanged. H2O2 also increased levels of 8-isoprostanes, stable prostaglandin-like compounds formed by free-radical-induced peroxidation of arachidonic acid, and 8-isoprostane levels were elevated in esophagitis. The PGF2{alpha} analog 8-iso PGF2{alpha} caused little contraction of LES strips, but reduced PGF2{alpha} binding and contraction of normal LES. In esophagitis PGF2{alpha} binding and contraction were reduced in LES, suggesting that isoprostanes may contribute to reduction in tone in esophagitis. The data suggest that in esophagitis IL-1{beta} causes production of H2O2. H2O2 increases PGE2, which relaxes the LES, and 8-iso F2{alpha}, which blocks PGF2{alpha}-mediated contraction.




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