Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats

Abstract

Adrenomedullin is a vasodilator peptide that displays a variety of effects, such as hypotension and vasodilatation. The aim of this study was to test the effect of intravenous adrenomedullin on the motility pattern of the small intestine, and the functional involvement of adrenomedullin in endotoxin-induced small-intestinal motility disturbance. Jejunal motility was recorded in fasted conscious rats, using miniature strain-gauge force transducers sutured to the serosal surface of the small-intestinal wall. Intravenous administration of adrenomedullin at doses of 3, 6, and 10 microg/kg per min over 30 min disrupted phase 3 of the migrating motor complex, with the disruption lasting for 61.9 +/- 5.1, 52.2 +/- 10.6, and 74.1 +/- 25.2 min, respectively. The interval from drug administration to the onset of disruption decreased as the dose of adrenomedullin increased to 41.5 +/- 11.0, 11.6 +/- 3.4, and 0 min, respectively (P < 0.05). An increase in the motility index was also dose-dependent (P < 0.05) at these doses of adrenomedullin. Lipopolysaccharide (50 microg/kg) induced disruption of phase 3, which lasted for 138.7 +/- 5.4 min. Previous administration of the putative adrenomedullin-receptor antagonist, AM (22-52), at a 50 microg/kg dose, attenuated the disruption induced by lipopolysaccharide to 74.4 +/- 3.5 min (P < 0.01). Our findings (1) suggest that intravenous adrenomedullin causes small-intestinal motility disturbances, and (2) support the hypothesis that adrenomedullin overproduction plays an important role in lipopolysaccharide-induced disruption of the motility pattern in the small intestine in rats.