Influence of endotoxin on contractility in the rat gastric fundus

Abstract

The influence of in vivo treatment with E. coli lipopolysaccharide endotoxin on the contractility of the rat gastric fundus was studied. Four h after lipopolysaccharide treatment (20 mg/kg i.p.), the contractile responses to prostaglandin F 2 α in longitudinal muscle strips from the gastric fundus were not different from those in control animals, while the well-known decreased response to noradrenaline in rings of the thoracic aorta was confirmed. Incubation of the tissues with l-arginine did not depress the response to prostaglandin F 2 α in fundus strips of lipopolysaccharide-treated rats. Twelve h after lipopolysaccharide treatment (6.7 mg/kg i.p.), the prostaglandin F 2 α -induced contractions were consistently depressed. The impairment of the prostaglandin F 2 α -induced responses by lipopolysaccharide treatment was not reversed by the nitric oxide synthase inhibitors N G-nitro- l-arginine ( l-NNA, 10 −4 M), N G-nitro- l-arginine methyl ester ( l-NAME, 3×10 −4 M), aminoguanidine (10 −4 M) and l- N 6-1-iminoethyl-lysine ( l-NIL, 10 −4 M) nor by the cyclooxygenase inhibitor indomethacin (10 −5 M). The impairment was prevented by pretreating the animals with dexamethasone (5 mg/kg i.p.), which had no effect per se on the contractile response to prostaglandin F 2 α . Lipopolysaccharide treatment did not influence the contractile responses to KCl and serotonin. The nonadrenergic noncholinergic relaxant responses to transmural electrical stimulation were not influenced 4 h after lipopolysaccharide treatment but were moderately reduced after 12 h. The results illustrate that the selective impairment of prostaglandin F 2 α -induced contractions in the rat gastric fundus by lipopolysaccharide treatment is not mediated via generation of nitric oxide; downregulation of the prostaglandin F 2 α -receptor by lipopolysaccharide treatment might be involved.