The effect of adrenoceptor antagonists on the ileal brake mechanism in the rat

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Abstract
1 Studies were carried out in the rat to investigate the effect of adrenoceptor antagonists on stomach to caecum transit time under control conditions and during ileal infusion of Intralipid. Stomach to caecum transit time (SCTT) of the head of the meal was measured by use of environmental hydrogen analysis and the distribution of the meal was assessed by a scintigraphic technique. 2 Four adrenoceptor antagonists were used in these studies, the α1 antagonist prazosin, the α2 antagonist, idazoxan, the β1 antagonist atenolol and the β2 antagonist ICI 118551. 3 None of the antagonists affected SCTT of the head of the meal during ileal infusion of saline. However, the α1 and β1 antagonists significantly reversed (P < 0.05) the delay in SCTT induced by ileal infusion of Intralipid whereas the α2 antagonist, idazoxan, potentiated this delay (P < 0.05). 4 Study of the distribution of the radiolabelled meal showed that the Intralipid delayed SCTT by slowing both gastric emptying (P < 0.05) and small bowel transit (P < 0.05). 5 Prazosin delayed gastric emptying under control conditions (P < 0.001) but did not alter significantly the effect of ileal lipid on the distribution of the meal, 100 min or 200 min after gavage. Idazoxan delayed gastric emptying during ileal infusion of saline (P < 0.05) and produced a proximal shift in the geometric centre of the meal in the small intestine (P < 0.001) and despite the apparent potentiation of the ileal brake effect indicated by the hydrogen analysis, idazoxan increased the amount of radioactivity in the colon 200 min after gavage (P < 0.05). 6 The meal distribution was more compatible with the hydrogen analysis after administration of the β-adrenoceptor antagonists. The reversal of the lipid-induced delay in SCTT caused by atenolol was associated with more radioactivity in the large intestine 200 min after the gavage. ICI 118551 had no significant effects on either the distribution of the meal or the SCTT of the head of the meal. 7 In conclusion, the data confirm that the sympathetic nervous system normally modulates or mediates the mechanisms that influence gastrointestinal transit in the rat and suggest that these mechanisms may be involved in the ileal brake effect. Nevertheless the data also suggest that simple measurement of the transit of the head of the meal by use of environmental hydrogen analysis may sometimes give a misleading impression of the action of drugs on gastrointestinal transit of the bulk of a test meal.