The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using dexamethasone and methylene blue

Abstract

The nitric oxide might be a putative mediator of the decrease in gastric emptying induced by bacterial lipopolysaccharide in rats. For that, we evaluated the effect of the pretreatment intravenous with dexamethasone and methylene blue in the retardation process of gastric emptying induced by intravenous application of lipopolysaccharide in rats. Dexamethasone has been shown to inhibit the induction of NOS II (induced NO-synthase) while the methylene blue, that blocks the soluble guanylyl cyclase, inhibits nitric oxide synthases and, in addition, inactivates nitric oxide directly. Male Wistar rats, specific patogenic free, were used after a 24 hour fast and 1 hour-water withdrawn. The pretreatment was performed using dexamethasone solutions (3 and 6 mg/kg), methylene blue (2 mg/kg) or sterile vehicle. The treatment consisted in the application of lipopolysaccharide (50 mug/kg) or vehicle. The time period between the pretreatment and treatment was 10 minutes, excluding the study with dexamethasone 6 mg/kg that was 1 hour. The gastric emptying was evaluated 1 hour after the lipopolysaccharide application, except for two studies with dexamethasone 3 mg/kg in which the time periods were 2 and 8 hours. A saline solution containing phenol red was used as the test meal. The gastric emptying was determined by measuring gastric retention 10 minutes after the orogastric infusion of the test meal. The pretreatment with dexamethasone or methylene blue and treatment with vehicle did not have effect in the gastric emptying comparing to the control group. We found that pretreatment with dexamethasone in the studies for 1 hour and 2 hours did not interfere in the retardation of the gastric emptying produced by endotoxin. Nevertheless, in the eighth period study with this drug there was a significant reduction of gastric retention in the endotoxin-treated animals in relation to the unpretreated ones. Meanwhile, the pretreatment with the methylene blue completely blocked the action of endotoxin on the gastric emptying in rats. These results suggest a possible involvement of nitric oxide on the effect of lipopolysaccharide in rat gastric emptying.