INFLUENCE OF ENDOTOXIN ON CONTRACTILITY IN THE RAT GASTRIC FUNDUS

The influence of in vivo treatment with E. coli lipopolysaccharide end otoxin on the contractility of the rat gastric fundus was studied. Fou r h after lipopolysaccharide treatment (20 mg/kg i.p.), the contractil e responses to prostaglandin F-2 alpha in longitudinal muscle strips f rom the gastric fundus were not different from those in control animal s, while the well-known decreased response to noradrenaline in rings o f the thoracic aorta was confirmed. Incubation of the tissues with L-a rginine did not depress the response to prostaglandin F-2 alpha in fun dus strips of lipopolysaccharide-treated rats. Twelve h after Lipopoly saccharide treatment (6.7 mg/kg i.p.), the prostaglandin F-2 alpha-ind uced contractions were consistently depressed. The impairment of the p rostaglandin F-2 alpha-induced responses by lipopolysaccharide treatme nt 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-NAM E, 3 x 10(-4) M), aminoguanidine (10(-4) M) and L-(N)6-1-iminoethyl-ly sine (L-NIL, 10(-4) M) nor by the cyclooxygenase inhibitor indomethaci n (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 c ontractile response to prostaglandin F-2 alpha. Lipopolysaccharide tre atment did not influence the contractile responses to KCl and serotoni n. The nonadrenergic noncholinergic relaxant responses to transmural e lectrical stimulation were not influenced 4 h after lipopolysaccharide treatment but were moderately reduced after 12 h. The results illustr ate that the selective impairment of prostaglandin F-2 alpha-induced c ontractions in the rat gastric fundus by lipopolysaccharide treatment is not mediated via generation of nitric oxide; downregulation of the prostaglandin F-2 alpha-receptor by lipopolysaccharide treatment might be involved. (C) 1997 Elsevier Science B.V.