Effects of endotoxin-induced shock on withdrawal contractions in the Guinea-pig isolated ileum.

Abstract

1. Taking into consideration the effect of septic shock on releasing various mediators, the present study was undertaken in an attempt to elucidate the effect of endotoxin on naloxone-induced withdrawal contractions in the guinea-pig isolated ileum. 2. To induce withdrawal contractions, preparations removed either from saline- or endotoxin (2.5 mg/kg in 0.4 mL, i.p.)-treated animals were incubated for 5 min with morphine (40 micromol/L) and naloxone (50 micromol/L) was then applied. 3. In tissues removed from endotoxin-treated animals, a significant reduction in withdrawal contractions was observed. In control preparations, indomethacin (1 micromol/L for 15 min) significantly reduced naloxone-induced contractions, whereas N(G)-nitro-L-arginine methyl ester (L-NAME; 10 micromol/L for 15 min) had no effect. However, indomethacin pretreatment of tissues removed from endotoxin-treated animals did not modify the withdrawal contractions, whereas L-NAME pretreatment enhanced the amplitude of the withdrawal-induced contractions. 4. These results suggest that attenuation of the withdrawal contractions in guinea-pig isolated ileum induced by endotoxin-pretreatment may be due, in part, to the activation of an L-arginine-nitric oxide pathway.